rs2076837

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.356

Alfa AF: 0.397 Hom.: 2264

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2076837; hg19: chr11-14974585;