3-53813381-A-G

Position:

• chr3-53813381-A-G

Variant summary

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

The NM_001128840.3(CACNA1D):​c.*1975A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 152,212 control chromosomes in the GnomAD database, including 46,137 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 0.77 (46135 hom., cov: 33)
  • Exomes 𝑓: 0.63 (2 hom.)
• Consequence: CACNA1D NM_001128840.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582

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]

CHDH (HGNC:24288): (choline dehydrogenase) The protein encoded by this gene is a choline dehydrogenase that localizes to the mitochondrion. Variations in this gene can affect susceptibility to choline deficiency. A few transcript variants have been found for this gene, but the full-length nature of only one has been characterized to date. [provided by RefSeq, Dec 2010]

CACNA1D (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1D	NM_000720.4	c.*1975A>G		3_prime_UTR_variant	49/49	ENST00000288139.11	NP_000711.1
CACNA1D	NM_001128840.3	c.*1975A>G		3_prime_UTR_variant	48/48	ENST00000350061.11	NP_001122312.1
CHDH	NM_018397.5	c.*4396T>C		3_prime_UTR_variant	9/9	ENST00000315251.11	NP_060867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1D	ENST00000288139.11	c.*1975A>G		3_prime_UTR_variant	49/49	1	NM_000720.4	ENSP00000288139.3
CACNA1D	ENST00000350061.11	c.*1975A>G		3_prime_UTR_variant	48/48	1	NM_001128840.3	ENSP00000288133.5
CHDH	ENST00000315251	c.*4396T>C		3_prime_UTR_variant	9/9	1	NM_018397.5	ENSP00000319851.5

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117421 AN: 152086 Hom.: 46066 Cov.: 33

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.773

GnomAD4 exome AF: 0.625 AC: 5 AN: 8 Hom.: 2 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

Gnomad4 NFE exome AF: 0.625

GnomAD4 genome AF: 0.772 AC: 117550 AN: 152204 Hom.: 46135 Cov.: 33 AF XY: 0.775 AC XY: 57673 AN XY: 74408

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.775

Alfa AF: 0.736 Hom.: 9074

Bravo AF: 0.787

Asia WGS AF: 0.917 AC: 3189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.55

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: rs14165; hg19: chr3-53847408;