dbSNP rs774903834: CALCB:p.Pro38Gln (chr11-15075087-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000728.4(CALCB):c.113C>A(p.Pro38Gln) 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 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P38L) has been classified as Uncertain significance.

Frequency

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

Consequence

CALCB
NM_000728.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.171

Variant links:

Genes affected

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050814033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCB	NM_000728.4 link	c.113C>A	p.Pro38Gln	missense_variant	Exon 3 of 5	ENST00000324229.11	NP_000719.1	P10092

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CALCB	ENST00000324229.11 link	c.113C>A	p.Pro38Gln	missense_variant	Exon 3 of 5	1	NM_000728.4	ENSP00000346017.5	P10092
CALCB	ENST00000523376.5 link	c.146C>A	p.Pro49Gln	missense_variant	Exon 8 of 10	2		ENSP00000428882.1	E7ESF5
CALCB	ENST00000533448.1 link	c.113C>A	p.Pro38Gln	missense_variant	Exon 3 of 5	2		ENSP00000433490.1	P10092

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152202

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.9

DANN

Benign

0.92

DEOGEN2

Benign

0.094

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.59

T;.;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.051

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

.;M;M

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.064

Sift

Benign

0.49

T;T;T

Sift4G

Benign

0.62

T;T;T

Polyphen

0.0040

.;B;B

Vest4

0.17

MutPred

0.14

.;Loss of glycosylation at P38 (P = 0.0427);Loss of glycosylation at P38 (P = 0.0427);

MVP

0.030

MPC

0.12

ClinPred

0.062

GERP RS

-4.8

Varity_R

0.038

gMVP

0.11

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over