rs41281860

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001174089.2(SLC4A11):c.1611C>T(p.Asn537Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,742 control chromosomes in the GnomAD database, including 11,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 806 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10278 hom. )

Consequence

SLC4A11
NM_001174089.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0100

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 20-3229655-G-A is Benign according to our data. Variant chr20-3229655-G-A is described in ClinVar as Benign. ClinVar VariationId is 261997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A11	NM_001174089.2 link	c.1611C>T	p.Asn537Asn	synonymous_variant	Exon 14 of 20	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.1611C>T	p.Asn537Asn	synonymous_variant	Exon 14 of 20		NM_001174089.2	ENSP00000493503.1		Q8NBS3-3

Frequencies

GnomAD3 genomes

AF:

0.0906

AC:

13783

AN:

152180

Hom.:

807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0344

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.0911

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.0285

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.0828

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.0976

GnomAD2 exomes

AF:

0.0935

AC:

23433

AN:

250636

AF XY:

0.0935

show subpopulations

Gnomad AFR exome

AF:

0.0313

Gnomad AMR exome

AF:

0.0707

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.146

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.113

AC:

164700

AN:

1461444

Hom.:

10278

Cov.:

AF XY:

0.111

AC XY:

80547

AN XY:

727046

show subpopulations

African (AFR)

AF:

0.0305

AC:

1021

AN:

33476

American (AMR)

AF:

0.0744

AC:

3327

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

3540

AN:

26130

East Asian (EAS)

AF:

0.00464

AC:

184

AN:

39696

South Asian (SAS)

AF:

0.0291

AC:

2511

AN:

86250

European-Finnish (FIN)

AF:

0.142

AC:

7534

AN:

53102

Middle Eastern (MID)

AF:

0.0733

AC:

421

AN:

5742

European-Non Finnish (NFE)

AF:

0.126

AC:

139891

AN:

1111960

Other (OTH)

AF:

0.104

AC:

6271

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

11341

22682

34022

45363

56704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4792

9584

14376

19168

23960

<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:

0.0905

AC:

13782

AN:

152298

Hom.:

806

Cov.:

AF XY:

0.0898

AC XY:

6688

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0343

AC:

1428

AN:

41578

American (AMR)

AF:

0.0910

AC:

1393

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

441

AN:

3468

East Asian (EAS)

AF:

0.00328

AC:

AN:

5178

South Asian (SAS)

AF:

0.0290

AC:

140

AN:

4832

European-Finnish (FIN)

AF:

0.141

AC:

1501

AN:

10618

Middle Eastern (MID)

AF:

0.0788

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.126

AC:

8545

AN:

68004

Other (OTH)

AF:

0.0971

AC:

205

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

662

1325

1987

2650

3312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.110

Hom.:

525

Bravo

AF:

0.0837

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.128

EpiControl

AF:

0.127

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Corneal dystrophy-perceptive deafness syndrome

Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 21, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

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

- -

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

-0.75

CADD

Benign

3.6

(source)

DANN

Benign

0.70

PhyloP100

0.010

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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