rs4258076

Variant names:

• chr9-19664083-G-T
• rs4258076
• NM_020344.4:c.931-41784C>A

Variant summary

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

The NM_020344.4(SLC24A2):​c.931-41784C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,076 control chromosomes in the GnomAD database, including 7,883 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 0.31 (7883 hom., cov: 33)
• Consequence: SLC24A2 NM_020344.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.272
• Publications: 7 publications found

Genes affected

SLC24A2 (HGNC:10976): (solute carrier family 24 member 2) This gene encodes a member of the calcium/cation antiporter superfamily of transport proteins. The encoded protein belongs to the SLC24 branch of exchangers, which can mediate the extrusion of one Ca2+ ion and one K+ ion in exchange for four Na+ ions. This family member is a retinal cone/brain exchanger that can mediate a light-induced decrease in free Ca2+ concentration. This protein may also play a neuroprotective role during ischemic brain injury. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A2	NM_020344.4	c.931-41784C>A		intron_variant	Intron 2 of 10	ENST00000341998.7	NP_065077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A2	ENST00000341998.7	c.931-41784C>A		intron_variant	Intron 2 of 10	1	NM_020344.4	ENSP00000344801.1
SLC24A2	ENST00000286344.4	c.931-41784C>A		intron_variant	Intron 2 of 9	1		ENSP00000286344.3

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47831 AN: 151958 Hom.: 7876 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.0424

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.321

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.315 AC: 47869 AN: 152076 Hom.: 7883 Cov.: 33 AF XY: 0.308 AC XY: 22932 AN XY: 74344

African (AFR) AF: 0.362 AC: 15016 AN: 41472

American (AMR) AF: 0.250 AC: 3824 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1108 AN: 3468

East Asian (EAS) AF: 0.0425 AC: 220 AN: 5174

South Asian (SAS) AF: 0.180 AC: 865 AN: 4810

European-Finnish (FIN) AF: 0.344 AC: 3638 AN: 10562

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22251 AN: 67990

Other (OTH) AF: 0.317 AC: 668 AN: 2108

Alfa AF: 0.316 Hom.: 19384

Bravo AF: 0.311

Asia WGS AF: 0.131 AC: 459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.86
PhyloP100		0.27
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: rs4258076; hg19: chr9-19664081;