20-3234249-C-T

Position:

chr20-3234249-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001174089.2(SLC4A11):c.357G>A(p.Ala119Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,614,042 control chromosomes in the GnomAD database, including 522 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 70 hom., cov: 33)

Exomes 𝑓: 0.024 ( 452 hom. )

Consequence

SLC4A11
NM_001174089.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.22

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 20-3234249-C-T is Benign according to our data. Variant chr20-3234249-C-T is described in ClinVar as [Benign]. Clinvar id is 262000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-3234249-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.22 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0266 (4053/152304) while in subpopulation AFR AF= 0.0436 (1811/41562). AF 95% confidence interval is 0.0419. There are 70 homozygotes in gnomad4. There are 1920 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4053 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A11	NM_001174089.2 linkuse as main transcript	c.357G>A	p.Ala119Ala	synonymous_variant	5/20	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.357G>A	p.Ala119Ala	synonymous_variant	5/20		NM_001174089.2	ENSP00000493503.1		Q8NBS3-3

Frequencies

GnomAD3 genomes

AF:

0.0266

AC:

4050

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.00910

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.0241

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.0140

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0238

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0197

AC:

4956

AN:

251258

Hom.:

AF XY:

0.0196

AC XY:

2659

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0411

Gnomad AMR exome

AF:

0.00709

Gnomad ASJ exome

AF:

0.00437

Gnomad EAS exome

AF:

0.0263

Gnomad SAS exome

AF:

0.0190

Gnomad FIN exome

AF:

0.0159

Gnomad NFE exome

AF:

0.0221

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.0237

AC:

34622

AN:

1461738

Hom.:

452

Cov.:

AF XY:

0.0234

AC XY:

17033

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.0443

Gnomad4 AMR exome

AF:

0.00754

Gnomad4 ASJ exome

AF:

0.00455

Gnomad4 EAS exome

AF:

0.0206

Gnomad4 SAS exome

AF:

0.0178

Gnomad4 FIN exome

AF:

0.0153

Gnomad4 NFE exome

AF:

0.0251

Gnomad4 OTH exome

AF:

0.0252

GnomAD4 genome

AF:

0.0266

AC:

4053

AN:

152304

Hom.:

Cov.:

AF XY:

0.0258

AC XY:

1920

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0436

Gnomad4 AMR

AF:

0.00908

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.0239

Gnomad4 SAS

AF:

0.0199

Gnomad4 FIN

AF:

0.0140

Gnomad4 NFE

AF:

0.0238

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0248

Hom.:

Bravo

AF:

0.0273

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

EpiCase

AF:

0.0219

EpiControl

AF:

0.0204

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 30, 2019	- -
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-perceptive deafness syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Corneal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.9

DANN

Benign

0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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