rs8035639

Variant names:

• chr15-65652210-C-T
• rs8035639
• NM_004727.3:c.2884-432C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004727.3(SLC24A1):​c.2884-432C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 302,050 control chromosomes in the GnomAD database, including 45,533 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (27042 hom., cov: 31)
  • Exomes 𝑓: 0.48 (18491 hom.)
• Consequence: SLC24A1 NM_004727.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13
• Publications: 5 publications found

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):

• congenital stationary night blindness 1D

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.838 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A1	NM_004727.3	MANE Select	c.2884-432C>T		intron	N/A	NP_004718.1
	SLC24A1	NM_001301032.1		c.2830-432C>T		intron	N/A	NP_001287961.1
	SLC24A1	NM_001301031.1		c.2794-432C>T		intron	N/A	NP_001287960.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A1	ENST00000261892.11	TSL:1 MANE Select	c.2884-432C>T		intron	N/A	ENSP00000261892.6
	SLC24A1	ENST00000546330.1	TSL:1	c.2830-432C>T		intron	N/A	ENSP00000439190.1
	SLC24A1	ENST00000399033.8	TSL:1	c.2794-432C>T		intron	N/A	ENSP00000381991.4

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85970 AN: 151926 Hom.: 26999 Cov.: 31

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.478 AC: 71753 AN: 150006 Hom.: 18491 Cov.: 0 AF XY: 0.487 AC XY: 39102 AN XY: 80288

African (AFR) AF: 0.852 AC: 3807 AN: 4468

American (AMR) AF: 0.472 AC: 2536 AN: 5370

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1518 AN: 3858

East Asian (EAS) AF: 0.805 AC: 5024 AN: 6244

South Asian (SAS) AF: 0.548 AC: 13802 AN: 25176

European-Finnish (FIN) AF: 0.447 AC: 3189 AN: 7130

Middle Eastern (MID) AF: 0.489 AC: 278 AN: 568

European-Non Finnish (NFE) AF: 0.425 AC: 38081 AN: 89664

Other (OTH) AF: 0.467 AC: 3518 AN: 7528

GnomAD4 genome AF: 0.566 AC: 86078 AN: 152044 Hom.: 27042 Cov.: 31 AF XY: 0.565 AC XY: 41960 AN XY: 74300

African (AFR) AF: 0.845 AC: 35052 AN: 41480

American (AMR) AF: 0.453 AC: 6912 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1406 AN: 3470

East Asian (EAS) AF: 0.808 AC: 4179 AN: 5174

South Asian (SAS) AF: 0.566 AC: 2729 AN: 4822

European-Finnish (FIN) AF: 0.463 AC: 4885 AN: 10544

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29336 AN: 67966

Other (OTH) AF: 0.549 AC: 1158 AN: 2108

Alfa AF: 0.483 Hom.: 10358

Bravo AF: 0.579

Asia WGS AF: 0.673 AC: 2341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.045
DANN	Benign	0.41
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8035639; hg19: chr15-65944548;