20-3233935-C-T

Variant names:

• chr20-3233935-C-T
• rs3803956
• NM_001174089.2:c.591G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.38

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]

ACMG classification

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 rank	MANE	Protein	UniProt
SLC4A11	NM_001174089.2	c.591G>A	p.Ser197Ser	synonymous_variant	Exon 6 of 20	ENST00000642402.1	NP_001167560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1	c.591G>A	p.Ser197Ser	synonymous_variant	Exon 6 of 20		NM_001174089.2	ENSP00000493503.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26398 AN: 152028 Hom.: 2449 Cov.: 32

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

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.: 36 AF XY: 0.175 AC XY: 127071 AN XY: 726720

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.: 32 AF XY: 0.169 AC XY: 12581 AN XY: 74396

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

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 20, 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	-0.73
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

Other links and lift over

dbSNP: rs3803956; hg19: chr20-3214581; COSMIC: COSV66260805; COSMIC: COSV66260805;