20-3228437-G-A

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.2389-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,612,928 control chromosomes in the GnomAD database, including 15,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2542 hom., cov: 31)

Exomes 𝑓: 0.13 ( 13247 hom. )

Consequence

SLC4A11
NM_001174089.2 intron

Scores

Splicing: ADA: 0.00001559

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.473

Publications

10 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=-0.84).

BP6

Variant 20-3228437-G-A is Benign according to our data. Variant chr20-3228437-G-A is described in ClinVar as Benign. ClinVar VariationId is 261999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A11	NM_001174089.2 link	c.2389-9C>T		intron_variant	Intron 18 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.2389-9C>T		intron_variant	Intron 18 of 19		NM_001174089.2	ENSP00000493503.1		Q8NBS3-3

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25604

AN:

152006

Hom.:

2538

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.0639

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.118

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.170

GnomAD2 exomes

AF:

0.128

AC:

32070

AN:

250404

AF XY:

0.124

show subpopulations

Gnomad AFR exome

AF:

0.279

Gnomad AMR exome

AF:

0.0889

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.131

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.130

AC:

189529

AN:

1460804

Hom.:

13247

Cov.:

AF XY:

0.127

AC XY:

92415

AN XY:

726724

show subpopulations

African (AFR)

AF:

0.280

AC:

9364

AN:

33476

American (AMR)

AF:

0.0945

AC:

4225

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

3502

AN:

26126

East Asian (EAS)

AF:

0.136

AC:

5400

AN:

39696

South Asian (SAS)

AF:

0.0549

AC:

4731

AN:

86248

European-Finnish (FIN)

AF:

0.147

AC:

7709

AN:

52486

Middle Eastern (MID)

AF:

0.0967

AC:

558

AN:

5768

European-Non Finnish (NFE)

AF:

0.131

AC:

145803

AN:

1111904

Other (OTH)

AF:

0.136

AC:

8237

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

10650

21301

31951

42602

53252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5206

10412

15618

20824

26030

<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:

0.168

AC:

25626

AN:

152124

Hom.:

2542

Cov.:

AF XY:

0.167

AC XY:

12391

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.274

AC:

11379

AN:

41474

American (AMR)

AF:

0.130

AC:

1988

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

422

AN:

3472

East Asian (EAS)

AF:

0.121

AC:

621

AN:

5146

South Asian (SAS)

AF:

0.0646

AC:

312

AN:

4828

European-Finnish (FIN)

AF:

0.146

AC:

1547

AN:

10604

Middle Eastern (MID)

AF:

0.120

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.130

AC:

8811

AN:

67982

Other (OTH)

AF:

0.169

AC:

357

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1069

2137

3206

4274

5343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.150

Hom.:

927

Bravo

AF:

0.172

Asia WGS

AF:

0.111

AC:

386

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 08, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Corneal dystrophy-perceptive deafness syndrome

Benign:2

Nov 20, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 10, 2021

Genome-Nilou Lab

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 13, 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. -

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

-0.84

CADD

Benign

0.020

(source)

DANN

Benign

0.85

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

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