chr2-40220447-T-C

Position:

• chr2-40220447-T-C

Variant summary

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

The NM_021097.5(SLC8A1):​c.1809-41954A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 151,998 control chromosomes in the GnomAD database, including 27,644 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 0.60 (27641 hom., cov: 31)
  • Exomes 𝑓: 0.69 (3 hom.)
• Consequence: SLC8A1 NM_021097.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.864

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC8A1	NM_021097.5	c.1809-41954A>G		intron_variant		ENST00000332839.9	NP_066920.1
SLC8A1-AS1	NR_038441.1	n.122-31237T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC8A1	ENST00000332839.9	c.1809-41954A>G		intron_variant		1	NM_021097.5	ENSP00000332931	P4
SLC8A1-AS1	ENST00000599740.1	n.74-31237T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90511 AN: 151864 Hom.: 27628 Cov.: 31

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.634

GnomAD4 exome AF: 0.688 AC: 11 AN: 16 Hom.: 3 AF XY: 0.643 AC XY: 9 AN XY: 14

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.700

GnomAD4 genome AF: 0.596 AC: 90563 AN: 151982 Hom.: 27641 Cov.: 31 AF XY: 0.590 AC XY: 43848 AN XY: 74280

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.631

Alfa AF: 0.659 Hom.: 67255

Bravo AF: 0.602

Asia WGS AF: 0.456 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.75

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: rs2540904; hg19: chr2-40447587;