rs898408

Positions:

• chr3-53682957-G-A
• chr3-53682957-G-C
• chr3-53682957-G-T

Variant summary

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

The NM_000720.4(CACNA1D):​c.1220+9141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,092 control chromosomes in the GnomAD database, including 38,711 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 0.70 (38711 hom., cov: 32)
• Consequence: CACNA1D NM_000720.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

Genes affected

CACNA1D (HGNC:1391): (calcium voltage-gated channel subunit alpha1 D) Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, namely alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1D subunit. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1D	NM_000720.4	c.1220+9141G>A		intron_variant		ENST00000288139.11	NP_000711.1
CACNA1D	NM_001128840.3	c.1220+9831G>A		intron_variant		ENST00000350061.11	NP_001122312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1D	ENST00000288139.11	c.1220+9141G>A		intron_variant		1	NM_000720.4	ENSP00000288139	P2
CACNA1D	ENST00000350061.11	c.1220+9831G>A		intron_variant		1	NM_001128840.3	ENSP00000288133

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106675 AN: 151972 Hom.: 38645 Cov.: 32

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.651

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

GnomAD4 genome AF: 0.702 AC: 106804 AN: 152092 Hom.: 38711 Cov.: 32 AF XY: 0.710 AC XY: 52795 AN XY: 74338

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.896

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.653

Alfa AF: 0.589 Hom.: 2046

Bravo AF: 0.709

Asia WGS AF: 0.839 AC: 2920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.84

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: rs898408; hg19: chr3-53716984;