2-187354325-G-A

Variant names:

• chr2-187354325-G-A
• rs858750
• NM_005795.6:c.910-1993C>T

Variant summary

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

The NM_005795.6(CALCRL):​c.910-1993C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 151,746 control chromosomes in the GnomAD database, including 57,502 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 0.87 (57502 hom., cov: 29)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005795.6. 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
	CALCRL	NM_005795.6	MANE Select	c.910-1993C>T		intron	N/A	NP_005786.1
	CALCRL	NM_001271751.2		c.910-1993C>T		intron	N/A	NP_001258680.1
	CALCRL	NM_001369434.1		c.910-1993C>T		intron	N/A	NP_001356363.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCRL	ENST00000392370.8	TSL:1 MANE Select	c.910-1993C>T		intron	N/A	ENSP00000376177.3
	CALCRL	ENST00000409998.5	TSL:5	c.910-1993C>T		intron	N/A	ENSP00000386972.1
	CALCRL	ENST00000410068.5	TSL:2	c.910-1993C>T		intron	N/A	ENSP00000387190.1

Frequencies

GnomAD3 genomes AF: 0.869 AC: 131737 AN: 151628 Hom.: 57448 Cov.: 29

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.870

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

GnomAD4 genome AF: 0.869 AC: 131846 AN: 151746 Hom.: 57502 Cov.: 29 AF XY: 0.867 AC XY: 64290 AN XY: 74176

African (AFR) AF: 0.909 AC: 37656 AN: 41426

American (AMR) AF: 0.817 AC: 12413 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3160 AN: 3464

East Asian (EAS) AF: 0.751 AC: 3829 AN: 5098

South Asian (SAS) AF: 0.793 AC: 3815 AN: 4808

European-Finnish (FIN) AF: 0.884 AC: 9356 AN: 10582

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.865 AC: 58708 AN: 67862

Other (OTH) AF: 0.871 AC: 1840 AN: 2112

Alfa AF: 0.865 Hom.: 104440

Bravo AF: 0.866

Asia WGS AF: 0.790 AC: 2745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.038
DANN	Benign	0.61
PhyloP100		-2.6
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: rs858750; hg19: chr2-188219052;