chr20-3231073-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001174089.2(SLC4A11):c.1043-15A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,606,584 control chromosomes in the GnomAD database, including 165,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 13606 hom., cov: 32)

Exomes 𝑓: 0.45 ( 151812 hom. )

Consequence

SLC4A11
NM_001174089.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.16

Publications

12 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 -20 ACMG points.

BP4

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

BP6

Variant 20-3231073-T-G is Benign according to our data. Variant chr20-3231073-T-G is described in ClinVar as Benign. ClinVar VariationId is 261993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A11	NM_001174089.2 link	c.1043-15A>C		intron_variant	Intron 9 of 19	ENST00000642402.1	NP_001167560.1	Q8NBS3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1 link	c.1043-15A>C		intron_variant	Intron 9 of 19		NM_001174089.2	ENSP00000493503.1		Q8NBS3-3

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

63278

AN:

145596

Hom.:

13591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.525

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.483

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.442

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.438

GnomAD2 exomes

AF:

0.453

AC:

112844

AN:

248962

AF XY:

0.449

show subpopulations

Gnomad AFR exome

AF:

0.349

Gnomad AMR exome

AF:

0.535

Gnomad ASJ exome

AF:

0.507

Gnomad EAS exome

AF:

0.483

Gnomad FIN exome

AF:

0.429

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.458

GnomAD4 exome

AF:

0.454

AC:

662808

AN:

1460902

Hom.:

151812

Cov.:

AF XY:

0.452

AC XY:

328160

AN XY:

726790

show subpopulations

African (AFR)

AF:

0.304

AC:

9944

AN:

32734

American (AMR)

AF:

0.525

AC:

23471

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

13283

AN:

26136

East Asian (EAS)

AF:

0.445

AC:

17673

AN:

39694

South Asian (SAS)

AF:

0.374

AC:

32239

AN:

86244

European-Finnish (FIN)

AF:

0.433

AC:

23090

AN:

53356

Middle Eastern (MID)

AF:

0.508

AC:

2925

AN:

5762

European-Non Finnish (NFE)

AF:

0.462

AC:

513201

AN:

1111984

Other (OTH)

AF:

0.447

AC:

26982

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

26602

53204

79806

106408

133010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15412

30824

46236

61648

77060

<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:

0.435

AC:

63334

AN:

145682

Hom.:

13606

Cov.:

AF XY:

0.433

AC XY:

30912

AN XY:

71320

show subpopulations

African (AFR)

AF:

0.359

AC:

12665

AN:

35258

American (AMR)

AF:

0.489

AC:

7431

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

1796

AN:

3470

East Asian (EAS)

AF:

0.484

AC:

2496

AN:

5162

South Asian (SAS)

AF:

0.355

AC:

1711

AN:

4820

European-Finnish (FIN)

AF:

0.442

AC:

4676

AN:

10568

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.457

AC:

31023

AN:

67934

Other (OTH)

AF:

0.439

AC:

911

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1902

3803

5705

7606

9508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.343

Hom.:

3088

Bravo

AF:

0.421

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 06, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Corneal dystrophy

Benign:1

Jan 12, 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. -

Corneal dystrophy-perceptive deafness syndrome

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital hereditary endothelial dystrophy of cornea

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.013

(source)

DANN

Benign

0.47

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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