rs35984752

chr15-65625902-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004727.3(SLC24A1):c.1822G>A(p.Val608Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,613,992 control chromosomes in the GnomAD database, including 96 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. V608V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.015 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (50 hom.)
• Consequence: SLC24A1 NM_004727.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0680

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004285425).
• BP6: Variant 15-65625902-G-A is Benign according to our data. Variant chr15-65625902-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-65625902-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A1	NM_004727.3	c.1822G>A	p.Val608Ile	missense_variant	2/10	ENST00000261892.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A1	ENST00000261892.11	c.1822G>A	p.Val608Ile	missense_variant	2/10	1	NM_004727.3	P4

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2350 AN: 152204 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0542

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00390 AC: 972 AN: 249056 Hom.: 21 AF XY: 0.00303 AC XY: 410 AN XY: 135108

Gnomad AFR exome AF: 0.0551

Gnomad AMR exome AF: 0.00261

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00161 AC: 2348 AN: 1461670 Hom.: 50 Cov.: 34 AF XY: 0.00142 AC XY: 1033 AN XY: 727110

Gnomad4 AFR exome AF: 0.0549

Gnomad4 AMR exome AF: 0.00331

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000118

Gnomad4 OTH exome AF: 0.00341

GnomAD4 genome AF: 0.0155 AC: 2354 AN: 152322 Hom.: 46 Cov.: 32 AF XY: 0.0146 AC XY: 1084 AN XY: 74488

Gnomad4 AFR AF: 0.0542

Gnomad4 AMR AF: 0.00418

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00313 Hom.: 15

Bravo AF: 0.0174

ESP6500AA AF: 0.0516 AC: 213

ESP6500EA AF: 0.000118 AC: 1

ExAC AF: 0.00465 AC: 563

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Congenital stationary night blindness 1D Benign:1

Likely 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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	0.23
Dann	Benign	0.59
DEOGEN2	Benign	0.011	T;T;.;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.15	T;T;T;T;.;T
MetaRNN	Benign	0.0043	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.27	N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.20	T;T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T;T
Polyphen		0.0040	B;B;.;.;.;B
Vest4		0.025
MVP		0.20
MPC		0.18
ClinPred		0.0041	T
GERP RS		-2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.028
gMVP		0.23

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

Other links and lift over

dbSNP: rs35984752; hg19: chr15-65918240; COSMIC: COSV99029403; COSMIC: COSV99029403;