rs34363823

Positions:

chr15-65625011-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000261892.11(SLC24A1):c.931G>C(p.Val311Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00796 in 1,612,910 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 30 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 115 hom. )

Consequence

SLC24A1
ENST00000261892.11 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.934

Variant links:

Genes affected

SLC24A1 (HGNC:10975): (solute carrier family 24 member 1) This gene encodes a member of the potassium-dependent sodium/calcium exchanger protein family. The encoded protein plays an important role in sodium/calcium exchange in retinal rod and cone photoreceptors by mediating the extrusion of one calcium ion and one potassium ion in exchange for four sodium ions. Mutations in this gene may play a role in congenital stationary night blindness. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

SLC24A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034194887).

BP6

Variant 15-65625011-G-C is Benign according to our data. Variant chr15-65625011-G-C is described in ClinVar as [Benign]. Clinvar id is 195228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-65625011-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0122 (1851/152290) while in subpopulation SAS AF= 0.0402 (194/4828). AF 95% confidence interval is 0.0356. There are 30 homozygotes in gnomad4. There are 905 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A1	NM_004727.3 linkuse as main transcript	c.931G>C	p.Val311Leu	missense_variant	2/10	ENST00000261892.11	NP_004718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A1	ENST00000261892.11 linkuse as main transcript	c.931G>C	p.Val311Leu	missense_variant	2/10	1	NM_004727.3	ENSP00000261892	P4	O60721-1

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1847

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0283

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0399

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00469

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00963

AC:

2385

AN:

247668

Hom.:

AF XY:

0.0110

AC XY:

1478

AN XY:

134434

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.00360

Gnomad ASJ exome

AF:

0.00659

Gnomad EAS exome

AF:

0.000724

Gnomad SAS exome

AF:

0.0365

Gnomad FIN exome

AF:

0.00168

Gnomad NFE exome

AF:

0.00478

Gnomad OTH exome

AF:

0.00599

GnomAD4 exome

AF:

0.00752

AC:

10987

AN:

1460620

Hom.:

115

Cov.:

AF XY:

0.00834

AC XY:

6062

AN XY:

726558

show subpopulations

Gnomad4 AFR exome

AF:

0.0293

Gnomad4 AMR exome

AF:

0.00399

Gnomad4 ASJ exome

AF:

0.00588

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0360

Gnomad4 FIN exome

AF:

0.00128

Gnomad4 NFE exome

AF:

0.00531

Gnomad4 OTH exome

AF:

0.00902

GnomAD4 genome

AF:

0.0122

AC:

1851

AN:

152290

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

905

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0283

Gnomad4 AMR

AF:

0.00614

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0402

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00469

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00642

Hom.:

Bravo

AF:

0.0125

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.0295

AC:

116

ESP6500EA

AF:

0.00628

AC:

ExAC

AF:

0.0104

AC:

1256

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.00671

EpiControl

AF:

0.00617

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 11, 2015	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital stationary night blindness 1D

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

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.2

DANN

Benign

0.86

DEOGEN2

Benign

0.020

T;T;.;.;.;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.83

T;T;T;T;.;T

MetaRNN

Benign

0.0034

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

.;L;L;.;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.95

N;N;N;N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.013

D;D;D;D;D;D

Sift4G

Uncertain

0.035

D;D;D;D;D;D

Polyphen

0.89

P;B;.;.;.;B

Vest4

0.063

MPC

0.21

ClinPred

0.0013

GERP RS

0.28

Varity_R

0.092

gMVP

0.18

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