chr2-187395674-T-A

Variant names:

• chr2-187395674-T-A
• rs3771081
• NM_005795.6:c.-292-7918A>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.-292-7918A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,842 control chromosomes in the GnomAD database, including 23,229 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 0.55 (23229 hom., cov: 32)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 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.-292-7918A>T		intron	N/A	NP_005786.1
	CALCRL	NM_001271751.2		c.-127-7918A>T		intron	N/A	NP_001258680.1
	CALCRL	NM_001369434.1		c.-292-7918A>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.-292-7918A>T		intron	N/A	ENSP00000376177.3
	CALCRL	ENST00000409998.5	TSL:5	c.-292-7918A>T		intron	N/A	ENSP00000386972.1
	CALCRL	ENST00000410068.5	TSL:2	c.-127-7918A>T		intron	N/A	ENSP00000387190.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82815 AN: 151724 Hom.: 23220 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.546 AC: 82850 AN: 151842 Hom.: 23229 Cov.: 32 AF XY: 0.550 AC XY: 40847 AN XY: 74212

African (AFR) AF: 0.443 AC: 18352 AN: 41430

American (AMR) AF: 0.653 AC: 9951 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1997 AN: 3468

East Asian (EAS) AF: 0.779 AC: 3991 AN: 5122

South Asian (SAS) AF: 0.481 AC: 2320 AN: 4820

European-Finnish (FIN) AF: 0.623 AC: 6586 AN: 10574

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37910 AN: 67888

Other (OTH) AF: 0.532 AC: 1120 AN: 2104

Alfa AF: 0.546 Hom.: 2865

Bravo AF: 0.551

Asia WGS AF: 0.598 AC: 2080 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	1.6
DANN	Benign	0.72
PhyloP100		-0.039
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: rs3771081; hg19: chr2-188260401;