rs2076837

Positions:

• chr11-14953039-G-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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCB	ENST00000523376.5	c.-445-24852G>A		intron_variant		2

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;