Variant 20-3233935-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001174089.2(SLC4A11):c.591G>A(p.Ser197Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,612,986 control chromosomes in the GnomAD database, including 25,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2447 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23334 hom. )

Consequence

SLC4A11
NM_001174089.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.38

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 links:

SLC4A11 (HGNC:):

SLC4A11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 20-3233935-C-T is Benign according to our data. Variant chr20-3233935-C-T is described in ClinVar as [Benign]. Clinvar id is 262002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A11	NM_001174089.2 linkuse as main transcript	c.591G>A	p.Ser197Ser	synonymous_variant	6/20	ENST00000642402.1	NP_001167560.1	Q8NBS3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1 linkuse as main transcript	c.591G>A	p.Ser197Ser	synonymous_variant	6/20		NM_001174089.2	ENSP00000493503.1		Q8NBS3-3

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26398

AN:

152028

Hom.:

2449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.0876

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.173

GnomAD3 exomes

AF:

0.153

AC:

38320

AN:

251130

Hom.:

3195

AF XY:

0.154

AC XY:

20894

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.0934

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.0987

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.176

AC:

257368

AN:

1460840

Hom.:

23334

Cov.:

AF XY:

0.175

AC XY:

127071

AN XY:

726720

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.0988

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.106

Gnomad4 NFE exome

AF:

0.185

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.174

AC:

26399

AN:

152146

Hom.:

2447

Cov.:

AF XY:

0.169

AC XY:

12581

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.211

Gnomad4 AMR

AF:

0.137

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.0876

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.175

Hom.:

1214

Bravo

AF:

0.177

Asia WGS

AF:

0.127

AC:

442

AN:

3478

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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 20, 2019	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Corneal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.48

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over