chr2-187378906-A-G

Position:

• chr2-187378906-A-G

Variant summary

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

The NM_005795.6(CALCRL):​c.500+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 1,253,112 control chromosomes in the GnomAD database, including 209,728 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 0.53 (22345 hom., cov: 32)
  • Exomes 𝑓: 0.58 (187383 hom.)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

Genes affected

CALCRL (HGNC:16709): (calcitonin receptor like receptor) Enables adrenomedullin binding activity; adrenomedullin receptor activity; and calcitonin gene-related peptide receptor activity. Involved in several processes, including G protein-coupled receptor signaling pathway; cellular response to sucrose stimulus; and receptor internalization. Located in endoplasmic reticulum; endosome; and lysosome. Part of CGRP receptor complex and adrenomedullin receptor complex. Colocalizes with plasma membrane. Implicated in hereditary lymphedema. [provided by Alliance of Genome Resources, Apr 2022]

CALCRL-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.500+34T>C		intron_variant		ENST00000392370.8	NP_005786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCRL	ENST00000392370.8	c.500+34T>C		intron_variant		1	NM_005795.6	ENSP00000376177.3

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81056 AN: 151796 Hom.: 22334 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.521

GnomAD3 exomes AF: 0.588 AC: 140870 AN: 239580 Hom.: 42740 AF XY: 0.577 AC XY: 75296 AN XY: 130466

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.747

Gnomad ASJ exome AF: 0.573

Gnomad EAS exome AF: 0.794

Gnomad SAS exome AF: 0.475

Gnomad FIN exome AF: 0.621

Gnomad NFE exome AF: 0.557

Gnomad OTH exome AF: 0.574

GnomAD4 exome AF: 0.578 AC: 636625 AN: 1101198 Hom.: 187383 Cov.: 14 AF XY: 0.572 AC XY: 322723 AN XY: 563896

Gnomad4 AFR exome AF: 0.406

Gnomad4 AMR exome AF: 0.732

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.816

Gnomad4 SAS exome AF: 0.477

Gnomad4 FIN exome AF: 0.615

Gnomad4 NFE exome AF: 0.573

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.534 AC: 81093 AN: 151914 Hom.: 22345 Cov.: 32 AF XY: 0.539 AC XY: 40036 AN XY: 74224

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.623

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.517

Alfa AF: 0.551 Hom.: 38547

Bravo AF: 0.537

Asia WGS AF: 0.594 AC: 2057 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3771084; hg19: chr2-188243633;