rs2076837

Variant names:

• chr11-14953039-G-A
• rs2076837
• ENST00000523376.5:c.-445-24852G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523376.5(CALCB):​c.-445-24852G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 150,820 control chromosomes in the GnomAD database, including 10,605 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 0.34 (10605 hom., cov: 31)
• Consequence: CALCB ENST00000523376.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCB	ENST00000523376.5	c.-445-24852G>A		intron_variant	Intron 5 of 9	2		ENSP00000428882.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51402 AN: 150706 Hom.: 10606 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.356

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.341 AC: 51408 AN: 150820 Hom.: 10605 Cov.: 31 AF XY: 0.338 AC XY: 24852 AN XY: 73634

African (AFR) AF: 0.117 AC: 4753 AN: 40524

American (AMR) AF: 0.513 AC: 7796 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1560 AN: 3460

East Asian (EAS) AF: 0.170 AC: 873 AN: 5136

South Asian (SAS) AF: 0.325 AC: 1560 AN: 4806

European-Finnish (FIN) AF: 0.282 AC: 2958 AN: 10502

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30635 AN: 67876

Other (OTH) AF: 0.356 AC: 751 AN: 2108

Alfa AF: 0.389 Hom.: 2269

Bravo AF: 0.344

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		-0.099
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2076837; hg19: chr11-14974585;