rs10179753

Positions:

• chr2-40547993-A-G

Variant summary

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

The XR_007086295.1(LOC101929667):​n.524+7555A>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 0.321 in 152,040 control chromosomes in the GnomAD database, including 8,481 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 0.32 (8481 hom., cov: 32)
• Consequence: LOC101929667 XR_007086295.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57

Genes affected

LOC101929667 (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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC101929667	XR_007086295.1	n.524+7555A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000405269.5	c.-25+62937T>C		intron_variant		5		ENSP00000385535

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48779 AN: 151922 Hom.: 8476 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.321 AC: 48787 AN: 152040 Hom.: 8481 Cov.: 32 AF XY: 0.312 AC XY: 23179 AN XY: 74316

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.350

Alfa AF: 0.385 Hom.: 15255

Bravo AF: 0.319

Asia WGS AF: 0.147 AC: 512 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	8.4
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10179753; hg19: chr2-40775133;