rs3771083

Variant names:

• chr2-187383867-A-G
• rs3771083
• NM_005795.6:c.52-562T>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.52-562T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 152,216 control chromosomes in the GnomAD database, including 694 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 0.087 (694 hom., cov: 32)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.52-562T>C		intron_variant	Intron 4 of 14	ENST00000392370.8	NP_005786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCRL	ENST00000392370.8	c.52-562T>C		intron_variant	Intron 4 of 14	1	NM_005795.6	ENSP00000376177.3

Frequencies

GnomAD3 genomes AF: 0.0871 AC: 13241 AN: 152098 Hom.: 690 Cov.: 32

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0640

Gnomad ASJ AF: 0.0453

Gnomad EAS AF: 0.0853

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.0870 AC: 13244 AN: 152216 Hom.: 694 Cov.: 32 AF XY: 0.0859 AC XY: 6392 AN XY: 74420

African (AFR) AF: 0.0602 AC: 2501 AN: 41552

American (AMR) AF: 0.0639 AC: 976 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0453 AC: 157 AN: 3468

East Asian (EAS) AF: 0.0851 AC: 440 AN: 5170

South Asian (SAS) AF: 0.170 AC: 823 AN: 4832

European-Finnish (FIN) AF: 0.0689 AC: 731 AN: 10602

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7341 AN: 67998

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.0892 Hom.: 87

Bravo AF: 0.0815

Asia WGS AF: 0.112 AC: 392 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	4.4
DANN	Benign	0.68
PhyloP100		0.71
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: rs3771083; hg19: chr2-188248594;