NM_021097.5:c.1809-41954A>G

Variant names:

• chr2-40220447-T-C
• rs2540904
• NM_021097.5:c.1809-41954A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021097.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A1	NM_021097.5	MANE Select	c.1809-41954A>G		intron	N/A	NP_066920.1
	SLC8A1	NM_001372263.2		c.1809-41954A>G		intron	N/A	NP_001359192.1
	SLC8A1	NM_001394103.1		c.1809-41954A>G		intron	N/A	NP_001381032.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC8A1	ENST00000332839.9	TSL:1 MANE Select	c.1809-41954A>G		intron	N/A	ENSP00000332931.4
	SLC8A1	ENST00000403092.5	TSL:1	c.1809-41954A>G		intron	N/A	ENSP00000384763.1
	SLC8A1	ENST00000405901.7	TSL:1	c.1809-41954A>G		intron	N/A	ENSP00000385678.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.700 AC: 7 AN: 10

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.492 AC: 20408 AN: 41448

American (AMR) AF: 0.664 AC: 10146 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2349 AN: 3472

East Asian (EAS) AF: 0.365 AC: 1870 AN: 5126

South Asian (SAS) AF: 0.507 AC: 2445 AN: 4820

European-Finnish (FIN) AF: 0.566 AC: 5978 AN: 10560

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45105 AN: 67968

Other (OTH) AF: 0.631 AC: 1328 AN: 2106

Alfa AF: 0.648 Hom.: 135085

Bravo AF: 0.602

Asia WGS AF: 0.456 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.6
DANN	Benign	0.75
PhyloP100		0.86
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: rs2540904; hg19: chr2-40447587;