rs3780215

Positions:

• chr9-19579429-G-A
• chr9-19579429-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020344.4(SLC24A2):​c.1130-2407C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,928 control chromosomes in the GnomAD database, including 6,819 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 0.27 (6819 hom., cov: 32)
• Consequence: SLC24A2 NM_020344.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A2	NM_020344.4	c.1130-2407C>T		intron_variant		ENST00000341998.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A2	ENST00000341998.7	c.1130-2407C>T		intron_variant		1	NM_020344.4	P3
SLC24A2	ENST00000286344.4	c.1079-2407C>T		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41056 AN: 151810 Hom.: 6793 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.271 AC: 41119 AN: 151928 Hom.: 6819 Cov.: 32 AF XY: 0.268 AC XY: 19889 AN XY: 74264

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.267

Alfa AF: 0.188 Hom.: 3972

Bravo AF: 0.283

Asia WGS AF: 0.242 AC: 838 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.9
DANN	Benign	0.44

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: rs3780215; hg19: chr9-19579427; COSMIC: COSV53874615;