chr2-40530651-A-G

Position:

• chr2-40530651-A-G

Variant summary

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

The ENST00000703001.1(ENSG00000287255):​n.167-2538A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0733 in 152,218 control chromosomes in the GnomAD database, including 940 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 0.073 (940 hom., cov: 32)
• Consequence: ENST00000703001.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322

Genes affected

(HGNC:):

SLC8A1 (HGNC:11068): (solute carrier family 8 member A1) In cardiac myocytes, Ca(2+) concentrations alternate between high levels during contraction and low levels during relaxation. The increase in Ca(2+) concentration during contraction is primarily due to release of Ca(2+) from intracellular stores. However, some Ca(2+) also enters the cell through the sarcolemma (plasma membrane). During relaxation, Ca(2+) is sequestered within the intracellular stores. To prevent overloading of intracellular stores, the Ca(2+) that entered across the sarcolemma must be extruded from the cell. The Na(+)-Ca(2+) exchanger is the primary mechanism by which the Ca(2+) is extruded from the cell during relaxation. In the heart, the exchanger may play a key role in digitalis action. The exchanger is the dominant mechanism in returning the cardiac myocyte to its resting state following excitation.[supplied by OMIM, Apr 2004]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC101929667	XR_007086295.1	n.167-2538A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000703001.1	n.167-2538A>G		intron_variant, non_coding_transcript_variant
SLC8A1	ENST00000405269.5	c.-25+80279T>C		intron_variant		5
	ENST00000688930.1	n.263-2538A>G		intron_variant, non_coding_transcript_variant
	ENST00000703033.1	n.247-2538A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0733 AC: 11142 AN: 152100 Hom.: 938 Cov.: 32

Gnomad AFR AF: 0.0568

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.0880

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

GnomAD4 genome AF: 0.0733 AC: 11152 AN: 152218 Hom.: 940 Cov.: 32 AF XY: 0.0771 AC XY: 5737 AN XY: 74408

Gnomad4 AFR AF: 0.0568

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0522

Gnomad4 NFE AF: 0.0432

Gnomad4 OTH AF: 0.0876

Alfa AF: 0.0591 Hom.: 521

Bravo AF: 0.0840

Asia WGS AF: 0.277 AC: 962 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.6
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13017846; hg19: chr2-40757791;