chr2-187404204-C-G

Variant names:

• chr2-187404204-C-G
• rs3821181
• NM_005795.6:c.-292-16448G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005795.6(CALCRL):​c.-292-16448G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,798 control chromosomes in the GnomAD database, including 2,372 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 0.15 (2372 hom., cov: 32)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 4 publications found

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:55863): (CALCRL and TFPI antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.-292-16448G>C		intron_variant	Intron 1 of 14	ENST00000392370.8	NP_005786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCRL	ENST00000392370.8	c.-292-16448G>C		intron_variant	Intron 1 of 14	1	NM_005795.6	ENSP00000376177.3

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22853 AN: 151680 Hom.: 2371 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.151 AC: 22852 AN: 151798 Hom.: 2372 Cov.: 32 AF XY: 0.157 AC XY: 11661 AN XY: 74166

African (AFR) AF: 0.0365 AC: 1513 AN: 41450

American (AMR) AF: 0.179 AC: 2723 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3466

East Asian (EAS) AF: 0.398 AC: 2044 AN: 5136

South Asian (SAS) AF: 0.110 AC: 529 AN: 4816

European-Finnish (FIN) AF: 0.299 AC: 3153 AN: 10544

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11898 AN: 67868

Other (OTH) AF: 0.140 AC: 296 AN: 2112

Alfa AF: 0.0865 Hom.: 166

Bravo AF: 0.138

Asia WGS AF: 0.220 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3821181; hg19: chr2-188268931;