Variant 3-53495165-G-GGAT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_000720.4(CACNA1D):c.20_22dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,606,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

CACNA1D
NM_000720.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.69

Variant links:

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]

CACNA1D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000231 (35/151204) while in subpopulation AFR AF= 0.000486 (20/41140). AF 95% confidence interval is 0.000322. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1D	NM_000720.4 linkuse as main transcript	c.20_22dup		5_prime_UTR_variant	1/49	ENST00000288139.11
CACNA1D	NM_001128840.3 linkuse as main transcript	c.20_22dup		5_prime_UTR_variant	1/48	ENST00000350061.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1D	ENST00000288139.11 linkuse as main transcript	c.20_22dup		5_prime_UTR_variant	1/49	1	NM_000720.4	P2	Q01668-2
CACNA1D	ENST00000350061.11 linkuse as main transcript	c.20_22dup		5_prime_UTR_variant	1/48	1	NM_001128840.3		Q01668-1

Frequencies

GnomAD3 genomes

AF:

0.000231

AC:

AN:

151204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000162

AC:

AN:

247184

Hom.:

AF XY:

0.000186

AC XY:

AN XY:

134164

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000383

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000199

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000204

AC:

297

AN:

1455684

Hom.:

Cov.:

AF XY:

0.000224

AC XY:

162

AN XY:

724360

show subpopulations

Gnomad4 AFR exome

AF:

0.000569

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000757

Gnomad4 NFE exome

AF:

0.000210

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.000231

AC:

AN:

151204

Hom.:

Cov.:

AF XY:

0.000285

AC XY:

AN XY:

73798

show subpopulations

Gnomad4 AFR

AF:

0.000486

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 05, 2022

Unlikely to be causative of primary aldosteronism, seizures, and neurologic abnormalities (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Nov 08, 2023

In-frame duplication in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over