rs8035639

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A1	NM_004727.3	c.2884-432C>T		intron_variant	Intron 8 of 9	ENST00000261892.11	NP_004718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A1	ENST00000261892.11	c.2884-432C>T		intron_variant	Intron 8 of 9	1	NM_004727.3	ENSP00000261892.6

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

Gnomad4 AFR exome AF: 0.852

Gnomad4 AMR exome AF: 0.472

Gnomad4 ASJ exome AF: 0.393

Gnomad4 EAS exome AF: 0.805

Gnomad4 SAS exome AF: 0.548

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.467

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

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.549

Alfa AF: 0.482 Hom.: 9261

Bravo AF: 0.579

Asia WGS AF: 0.673 AC: 2341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.045
DANN	Benign	0.41

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: rs8035639; hg19: chr15-65944548;