11-14972978-A-G

Variant names:

• chr11-14972978-A-G
• rs3781719
• ENST00000523376.5:c.-445-4913A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000523376.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCB	ENST00000523376.5	TSL:2	c.-445-4913A>G		intron	N/A	ENSP00000428882.1
	CALCB	ENST00000887807.1		c.-478-4913A>G		intron	N/A	ENSP00000557866.1

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

African (AFR) AF: 0.404 AC: 16740 AN: 41486

American (AMR) AF: 0.433 AC: 6617 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 914 AN: 3470

East Asian (EAS) AF: 0.186 AC: 963 AN: 5166

South Asian (SAS) AF: 0.278 AC: 1342 AN: 4820

European-Finnish (FIN) AF: 0.241 AC: 2551 AN: 10584

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21978 AN: 67950

Other (OTH) AF: 0.321 AC: 677 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.49
PhyloP100		-0.37
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: rs3781719; hg19: chr11-14994524;