20-3234173-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001174089.2(SLC4A11):c.433A>C(p.Arg145Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,613,864 control chromosomes in the GnomAD database, including 145,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.49 ( 18893 hom., cov: 33)

Exomes 𝑓: 0.41 ( 126459 hom. )

Consequence

SLC4A11
NM_001174089.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:9

Conservation

PhyloP100: 0.824

Publications

34 publications found

Variant links:

Genes affected

SLC4A11 (HGNC:16438): (solute carrier family 4 member 11) This gene encodes a voltage-regulated, electrogenic sodium-coupled borate cotransporter that is essential for borate homeostasis, cell growth and cell proliferation. Mutations in this gene have been associated with a number of endothelial corneal dystrophies including recessive corneal endothelial dystrophy 2, corneal dystrophy and perceptive deafness, and Fuchs endothelial corneal dystrophy. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2010]

SLC4A11 Gene-Disease associations (from GenCC):

corneal dystrophy, Fuchs endothelial, 4
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
congenital hereditary endothelial dystrophy of cornea
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
corneal dystrophy-perceptive deafness syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
Fuchs' endothelial dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SLC4A11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 20-3234173-T-G is Benign according to our data. Variant chr20-3234173-T-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 262001.

BP7

Synonymous conserved (PhyloP=0.824 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A11	NM_001174089.2 link	c.433A>C	p.Arg145Arg	synonymous_variant	Exon 5 of 20	ENST00000642402.1	NP_001167560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1 link	c.433A>C	p.Arg145Arg	synonymous_variant	Exon 5 of 20		NM_001174089.2	ENSP00000493503.1

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73785

AN:

151990

Hom.:

18868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.647

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.522

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.442

GnomAD2 exomes

AF:

0.438

AC:

109986

AN:

251272

AF XY:

0.426

show subpopulations

Gnomad AFR exome

AF:

0.655

Gnomad AMR exome

AF:

0.464

Gnomad ASJ exome

AF:

0.380

Gnomad EAS exome

AF:

0.577

Gnomad FIN exome

AF:

0.513

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.411

AC:

600783

AN:

1461756

Hom.:

126459

Cov.:

AF XY:

0.408

AC XY:

296498

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.653

AC:

21848

AN:

33480

American (AMR)

AF:

0.460

AC:

20576

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.381

AC:

9962

AN:

26136

East Asian (EAS)

AF:

0.548

AC:

21749

AN:

39700

South Asian (SAS)

AF:

0.315

AC:

27179

AN:

86258

European-Finnish (FIN)

AF:

0.505

AC:

26927

AN:

53310

Middle Eastern (MID)

AF:

0.384

AC:

2217

AN:

5768

European-Non Finnish (NFE)

AF:

0.400

AC:

444509

AN:

1111990

Other (OTH)

AF:

0.427

AC:

25816

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

25598

51197

76795

102394

127992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13884

27768

41652

55536

69420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.486

AC:

73854

AN:

152108

Hom.:

18893

Cov.:

AF XY:

0.489

AC XY:

36336

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.647

AC:

26874

AN:

41512

American (AMR)

AF:

0.472

AC:

7222

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

1291

AN:

3466

East Asian (EAS)

AF:

0.569

AC:

2927

AN:

5146

South Asian (SAS)

AF:

0.331

AC:

1595

AN:

4820

European-Finnish (FIN)

AF:

0.522

AC:

5528

AN:

10598

Middle Eastern (MID)

AF:

0.360

AC:

105

AN:

292

European-Non Finnish (NFE)

AF:

0.397

AC:

26963

AN:

67948

Other (OTH)

AF:

0.441

AC:

932

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1936

3872

5808

7744

9680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.405

Hom.:

18761

Bravo

AF:

0.491

Asia WGS

AF:

0.411

AC:

1432

AN:

3478

EpiCase

AF:

0.386

EpiControl

AF:

0.399

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:9

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Corneal dystrophy-perceptive deafness syndrome

Benign:3

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 19, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Oct 04, 2021

Molecular Genetics, Royal Melbourne Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Population allele frequency is 44% (rs3827075, 122,773/276,940 alleles in gnomAD v2.0.2). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1

Congenital hereditary endothelial dystrophy of cornea

Uncertain:1Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Aug 07, 2022

Prof. Brien Holden Eye Research Center, Hyderabad Eye Research Foundation, L V Prasad Eye Institute

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:case-control

Opaque cornea with reduced visual acuity. This change was observed with the other variant (NM_032034.4:c.[2413_2414insT]).

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Corneal dystrophy

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.5

(source)

DANN

Benign

0.45

PhyloP100

0.82

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over