9-19623128-T-C

Variant names:

• chr9-19623128-T-C
• rs10757082
• NM_020344.4:c.931-829A>G

Variant summary

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

The NM_020344.4(SLC24A2):​c.931-829A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,092 control chromosomes in the GnomAD database, including 43,078 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 0.75 (43078 hom., cov: 32)
• Consequence: SLC24A2 NM_020344.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020344.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A2	NM_020344.4	MANE Select	c.931-829A>G		intron	N/A	NP_065077.1
	SLC24A2	NM_001375850.1		c.931-829A>G		intron	N/A	NP_001362779.1
	SLC24A2	NM_001193288.3		c.931-829A>G		intron	N/A	NP_001180217.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A2	ENST00000341998.7	TSL:1 MANE Select	c.931-829A>G		intron	N/A	ENSP00000344801.1
	SLC24A2	ENST00000286344.4	TSL:1	c.931-829A>G		intron	N/A	ENSP00000286344.3

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114229 AN: 151974 Hom.: 43023 Cov.: 32

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.874

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.752 AC: 114343 AN: 152092 Hom.: 43078 Cov.: 32 AF XY: 0.754 AC XY: 56010 AN XY: 74308

African (AFR) AF: 0.761 AC: 31557 AN: 41470

American (AMR) AF: 0.779 AC: 11893 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.711 AC: 2469 AN: 3472

East Asian (EAS) AF: 0.873 AC: 4517 AN: 5172

South Asian (SAS) AF: 0.791 AC: 3810 AN: 4818

European-Finnish (FIN) AF: 0.768 AC: 8133 AN: 10584

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49589 AN: 67986

Other (OTH) AF: 0.741 AC: 1564 AN: 2110

Alfa AF: 0.732 Hom.: 59064

Bravo AF: 0.753

Asia WGS AF: 0.842 AC: 2929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.9
DANN	Benign	0.60
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10757082; hg19: chr9-19623126; COSMIC: COSV53860449;