11-14972978-A-G

Position:

• chr11-14972978-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523376.5(CALCB):​c.-445-4913A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,078 control chromosomes in the GnomAD database, including 9,230 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 (9230 hom., cov: 32)
• Consequence: CALCB ENST00000523376.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.14972978A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCB	ENST00000523376.5	c.-445-4913A>G		intron_variant		2		ENSP00000428882.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52112 AN: 151960 Hom.: 9226 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.343 AC: 52176 AN: 152078 Hom.: 9230 Cov.: 32 AF XY: 0.342 AC XY: 25389 AN XY: 74330

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.321

Alfa AF: 0.340 Hom.: 1399

Bravo AF: 0.358

Asia WGS AF: 0.271 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3781719; hg19: chr11-14994524;