NM_020344.4:c.1130-2407C>T

Variant names:

• chr9-19579429-G-A
• rs3780215
• NM_020344.4:c.1130-2407C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 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.1130-2407C>T		intron	N/A	NP_065077.1
	SLC24A2	NM_001375850.1		c.1130-2407C>T		intron	N/A	NP_001362779.1
	SLC24A2	NM_001193288.3		c.1079-2407C>T		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.1130-2407C>T		intron	N/A	ENSP00000344801.1
	SLC24A2	ENST00000286344.4	TSL:1	c.1079-2407C>T		intron	N/A	ENSP00000286344.3

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

African (AFR) AF: 0.471 AC: 19507 AN: 41388

American (AMR) AF: 0.219 AC: 3336 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 851 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1560 AN: 5148

South Asian (SAS) AF: 0.143 AC: 686 AN: 4810

European-Finnish (FIN) AF: 0.202 AC: 2134 AN: 10568

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12319 AN: 67962

Other (OTH) AF: 0.267 AC: 566 AN: 2116

Alfa AF: 0.216 Hom.: 8235

Bravo AF: 0.283

Asia WGS AF: 0.242 AC: 838 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.9
DANN	Benign	0.44
PhyloP100		0.46
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: rs3780215; hg19: chr9-19579427; COSMIC: COSV53874615;