15-65625902-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 16/21 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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0680

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

inherited retinal dystrophy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
congenital stationary night blindness 1D
Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
congenital stationary night blindness
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SLC24A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 259526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0523 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004727.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC24A1	NM_004727.3	MANE Select	c.1822G>A	p.Val608Ile	missense	Exon 2 of 10	NP_004718.1	O60721-1
SLC24A1	NM_001301032.1		c.1822G>A	p.Val608Ile	missense	Exon 1 of 8	NP_001287961.1	O60721-2
SLC24A1	NM_001301031.1		c.1822G>A	p.Val608Ile	missense	Exon 1 of 8	NP_001287960.1	B4E1W0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC24A1	ENST00000261892.11	TSL:1 MANE Select	c.1822G>A	p.Val608Ile	missense	Exon 2 of 10	ENSP00000261892.6	O60721-1
SLC24A1	ENST00000546330.1	TSL:1	c.1822G>A	p.Val608Ile	missense	Exon 1 of 8	ENSP00000439190.1	O60721-2
SLC24A1	ENST00000399033.8	TSL:1	c.1822G>A	p.Val608Ile	missense	Exon 1 of 8	ENSP00000381991.4	O60721-3

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2350

AN:

152204

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00390

AC:

972

AN:

249056

AF XY:

0.00303

show subpopulations

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 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.:

Cov.:

AF XY:

0.00142

AC XY:

1033

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.0549

AC:

1838

AN:

33476

American (AMR)

AF:

0.00331

AC:

148

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000162

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000118

AC:

131

AN:

1111866

Other (OTH)

AF:

0.00341

AC:

206

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

148

295

443

590

738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0155

AC:

2354

AN:

152322

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

1084

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0542

AC:

2252

AN:

41560

American (AMR)

AF:

0.00418

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68036

Other (OTH)

AF:

0.0109

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

111

222

333

444

555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00401

Hom.:

Bravo

AF:

0.0174

ESP6500AA

AF:

0.0516

AC:

213

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.00465

AC:

563

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Congenital stationary night blindness 1D (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.23

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.011

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

PhyloP100

-0.068

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.27

REVEL

Benign

0.15

Sift

Benign

0.20

Sift4G

Benign

0.20

Polyphen

0.0040

Vest4

0.025

MVP

0.20

MPC

0.18

ClinPred

0.0041

GERP RS

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.028

gMVP

0.23

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over