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):ā€‹c.433A>Cā€‹(p.Arg145Arg) 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: š‘“ 0.49 ( 18893 hom., cov: 33)
Exomes š‘“: 0.41 ( 126459 hom. )

Consequence

SLC4A11
NM_001174089.2 synonymous

Scores

2

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]

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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: {Uncertain_significance=1, Benign=8}.
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 rank MANE Protein UniProt
SLC4A11NM_001174089.2 linkc.433A>C p.Arg145Arg synonymous_variant Exon 5 of 20 ENST00000642402.1 NP_001167560.1 Q8NBS3-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC4A11ENST00000642402.1 linkc.433A>C p.Arg145Arg synonymous_variant Exon 5 of 20 NM_001174089.2 ENSP00000493503.1 Q8NBS3-3

Frequencies

GnomAD3 genomes
AF:
0.485
AC:
73785
AN:
151990
Hom.:
18868
Cov.:
33
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.:
73
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.:
33
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
Jul 10, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Nov 19, 2019
Natera, Inc.
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Oct 04, 2021
Molecular Genetics, Royal Melbourne Hospital
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
Aug 07, 2022
Prof. Brien Holden Eye Research Center, Hyderabad Eye Research Foundation, L V Prasad Eye Institute
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: case-control

Opaque cornea with reduced visual acuity. This change was observed with the other variant (NM_032034.4:c.[2413_2414insT]). -

Jul 10, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:2
Dec 03, 2021
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
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

- -

Corneal dystrophy Benign:1
Mar 06, 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. -

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.

Other links and lift over

dbSNP: rs3827075; hg19: chr20-3214819; COSMIC: COSV66261640; COSMIC: COSV66261640; API