Variant 11-14967729-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001033953.3(CALCA):c.353C>T(p.Ala118Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CALCA
NM_001033953.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

CALCA (HGNC:1437): (calcitonin related polypeptide alpha) This gene encodes the peptide hormones calcitonin, calcitonin gene-related peptide and katacalcin by tissue-specific alternative RNA splicing of the gene transcripts and cleavage of inactive precursor proteins. Calcitonin is involved in calcium regulation and acts to regulate phosphorus metabolism. Calcitonin gene-related peptide functions as a vasodilator and as an antimicrobial peptide while katacalcin is a calcium-lowering peptide. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2014]

CALCA links:

CALCA (HGNC:):

CALCA links:

CALCB (HGNC:1438): (calcitonin related polypeptide beta) Predicted to enable calcitonin receptor binding activity. Predicted to be involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway and regulation of cytosolic calcium ion concentration. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

CALCB links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09326708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
CALCA	NM_001033953.3 linkuse as main transcript	c.353C>T	p.Ala118Val	missense_variant	4/5	NP_001029125.1	P06881-1
CALCA	NM_001378950.1 linkuse as main transcript	c.353C>T	p.Ala118Val	missense_variant	4/5	NP_001365879.1
CALCA	NR_125898.2 linkuse as main transcript	n.641C>T		non_coding_transcript_exon_variant	5/6
CALCA	NR_166196.1 linkuse as main transcript	n.665C>T		non_coding_transcript_exon_variant	5/6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
CALCA	ENST00000469608.5 linkuse as main transcript	n.*99C>T	non_coding_transcript_exon_variant	5/6	1	ENSP00000420618.1	P01258-2
CALCA	ENST00000494746.1 linkuse as main transcript	n.1351C>T	non_coding_transcript_exon_variant	2/3	1
CALCA	ENST00000469608.5 linkuse as main transcript	n.*99C>T	3_prime_UTR_variant	5/6	1	ENSP00000420618.1	P01258-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2024

The c.353C>T (p.A118V) alteration is located in exon 4 (coding exon 3) of the CALCA gene. This alteration results from a C to T substitution at nucleotide position 353, causing the alanine (A) at amino acid position 118 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.3

DANN

Benign

0.96

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.72

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.86

.;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.093

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M

PROVEAN

Benign

-0.93

N;N

REVEL

Benign

0.031

Sift

Benign

0.21

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.025

B;B

Vest4

0.12

MVP

0.014

ClinPred

0.11

GERP RS

1.3

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

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