rs41281860

Positions:

• chr20-3229655-G-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.1611C>T​(p.Asn537=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0100

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=-0.75).
• BP6: Variant 20-3229655-G-A is Benign according to our data. Variant chr20-3229655-G-A is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
SLC4A11	NM_001174089.2	c.1611C>T	p.Asn537=	synonymous_variant	14/20	ENST00000642402.1	NP_001167560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1	c.1611C>T	p.Asn537=	synonymous_variant	14/20		NM_001174089.2	ENSP00000493503	P2

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13783 AN: 152180 Hom.: 807 Cov.: 33

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

GnomAD3 exomes AF: 0.0935 AC: 23433 AN: 250636 Hom.: 1375 AF XY: 0.0935 AC XY: 12694 AN XY: 135712

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 SAS exome AF: 0.0288

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.: 46 AF XY: 0.111 AC XY: 80547 AN XY: 727046

Gnomad4 AFR exome AF: 0.0305

Gnomad4 AMR exome AF: 0.0744

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.00464

Gnomad4 SAS exome AF: 0.0291

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.0905 AC: 13782 AN: 152298 Hom.: 806 Cov.: 33 AF XY: 0.0898 AC XY: 6688 AN XY: 74468

Gnomad4 AFR AF: 0.0343

Gnomad4 AMR AF: 0.0910

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.0971

Alfa AF: 0.111 Hom.: 524

Bravo AF: 0.0837

Asia WGS AF: 0.0180 AC: 62 AN: 3478

EpiCase AF: 0.128

EpiControl AF: 0.127

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

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 21, 2019	- -

not provided Benign:2

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

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	-0.75
CADD	Benign	3.6
DANN	Benign	0.70

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

LitVar

Other links and lift over

dbSNP: rs41281860; hg19: chr20-3210301; COSMIC: COSV66260334; COSMIC: COSV66260334;