chr20-3234173-T-G

Position:

chr20-3234173-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001174089.2(SLC4A11):c.433A>C(p.Arg145=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,613,864 control chromosomes in the GnomAD database, including 145,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.49 ( 18893 hom., cov: 33)

Exomes 𝑓: 0.41 ( 126459 hom. )

Consequence

SLC4A11
NM_001174089.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:9

Conservation

PhyloP100: 0.824

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 20-3234173-T-G is Benign according to our data. Variant chr20-3234173-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 262001.We mark this variant Likely_benign, oryginal submissions are: {Benign=8, Uncertain_significance=1}.

BP7

Synonymous conserved (PhyloP=0.824 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.641 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.433A>C	p.Arg145=	synonymous_variant	5/20	ENST00000642402.1	NP_001167560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A11	ENST00000642402.1 linkuse as main transcript	c.433A>C	p.Arg145=	synonymous_variant	5/20		NM_001174089.2	ENSP00000493503	P2	Q8NBS3-3

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73785

AN:

151990

Hom.:

18868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.647

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.522

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.442

GnomAD3 exomes

AF:

0.438

AC:

109986

AN:

251272

Hom.:

25175

AF XY:

0.426

AC XY:

57926

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.655

Gnomad AMR exome

AF:

0.464

Gnomad ASJ exome

AF:

0.380

Gnomad EAS exome

AF:

0.577

Gnomad SAS exome

AF:

0.311

Gnomad FIN exome

AF:

0.513

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.411

AC:

600783

AN:

1461756

Hom.:

126459

Cov.:

AF XY:

0.408

AC XY:

296498

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.653

Gnomad4 AMR exome

AF:

0.460

Gnomad4 ASJ exome

AF:

0.381

Gnomad4 EAS exome

AF:

0.548

Gnomad4 SAS exome

AF:

0.315

Gnomad4 FIN exome

AF:

0.505

Gnomad4 NFE exome

AF:

0.400

Gnomad4 OTH exome

AF:

0.427

GnomAD4 genome

AF:

0.486

AC:

73854

AN:

152108

Hom.:

18893

Cov.:

AF XY:

0.489

AC XY:

36336

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.647

Gnomad4 AMR

AF:

0.472

Gnomad4 ASJ

AF:

0.372

Gnomad4 EAS

AF:

0.569

Gnomad4 SAS

AF:

0.331

Gnomad4 FIN

AF:

0.522

Gnomad4 NFE

AF:

0.397

Gnomad4 OTH

AF:

0.441

Alfa

AF:

0.401

Hom.:

14289

Bravo

AF:

0.491

Asia WGS

AF:

0.411

AC:

1432

AN:

3478

EpiCase

AF:

0.386

EpiControl

AF:

0.399

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:9

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Corneal dystrophy-perceptive deafness syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 19, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Genetics, Royal Melbourne Hospital	Oct 04, 2021	Population allele frequency is 44% (rs3827075, 122,773/276,940 alleles in gnomAD v2.0.2). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1 -

Congenital hereditary endothelial dystrophy of cornea

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	case-control	Prof. Brien Holden Eye Research Center, Hyderabad Eye Research Foundation, L V Prasad Eye Institute	Aug 07, 2022	Opaque cornea with reduced visual acuity. This change was observed with the other variant (NM_032034.4:c.[2413_2414insT]). -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -

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	-	- -

Corneal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.5

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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