2-40255057-T-TTCATTCCCTCTCCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_021097.5(SLC8A1):c.1809-76565_1809-76564insTGGAGAGGGAATGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 151,864 control chromosomes in the GnomAD database, including 1,790 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1790 hom., cov: 30)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

Genes affected

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]

SLC8A1-AS1 (HGNC:44102): (SLC8A1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC8A1	NM_021097.5	c.1809-76565_1809-76564insTGGAGAGGGAATGA		intron_variant		ENST00000332839.9
SLC8A1-AS1	NR_038441.1	n.851_852insCATTCCCTCTCCAT		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC8A1	ENST00000332839.9	c.1809-76565_1809-76564insTGGAGAGGGAATGA		intron_variant		1	NM_021097.5	P4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20939 AN: 151740 Hom.: 1790 Cov.: 30

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.0624

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.138 AC: 20948 AN: 151858 Hom.: 1790 Cov.: 30 AF XY: 0.139 AC XY: 10294 AN XY: 74216

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.0621

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0854

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0426 Hom.: 17

Asia WGS AF: 0.116 AC: 404 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11274804; hg19: chr2-40482197;