11-15075180-A-C

Position:

• chr11-15075180-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000728.4(CALCB):​c.206A>C​(p.Gln69Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALCB NM_000728.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.967

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]

ACMG classification

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=0.08749768).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCB	NM_000728.4	c.206A>C	p.Gln69Pro	missense_variant	3/5	ENST00000324229.11	NP_000719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCB	ENST00000324229.11	c.206A>C	p.Gln69Pro	missense_variant	3/5	1	NM_000728.4	ENSP00000346017	P1
CALCB	ENST00000523376.5	c.239A>C	p.Gln80Pro	missense_variant	8/10	2		ENSP00000428882
CALCB	ENST00000533448.1	c.206A>C	p.Gln69Pro	missense_variant	3/5	2		ENSP00000433490	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2024

The c.206A>C (p.Q69P) alteration is located in exon 3 (coding exon 2) of the CALCB gene. This alteration results from a A to C substitution at nucleotide position 206, causing the glutamine (Q) at amino acid position 69 to be replaced by a proline (P). 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
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.18	T;T;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.33	T;.;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.087	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	.;M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.5	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.067	T;D;D
Sift4G	Benign	0.10	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.24
MutPred		0.26		.;Gain of glycosylation at Q69 (P = 0.0178);Gain of glycosylation at Q69 (P = 0.0178);
MVP		0.11
MPC		0.15
ClinPred		0.12	T
GERP RS		-3.1
Varity_R		0.49
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-15096726;