2-187412396-T-A

Variant names:

• chr2-187412396-T-A
• rs3771076
• NM_005795.6:c.-292-24640A>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.-292-24640A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,930 control chromosomes in the GnomAD database, including 10,478 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 0.37 (10478 hom., cov: 31)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• 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)

ENSG00000307603 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.-292-24640A>T		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.-292-24640A>T		intron_variant	Intron 1 of 14	1	NM_005795.6	ENSP00000376177.3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55739 AN: 151812 Hom.: 10461 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.367 AC: 55793 AN: 151930 Hom.: 10478 Cov.: 31 AF XY: 0.364 AC XY: 27033 AN XY: 74282

African (AFR) AF: 0.334 AC: 13821 AN: 41424

American (AMR) AF: 0.310 AC: 4730 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1372 AN: 3470

East Asian (EAS) AF: 0.153 AC: 791 AN: 5180

South Asian (SAS) AF: 0.442 AC: 2118 AN: 4796

European-Finnish (FIN) AF: 0.366 AC: 3868 AN: 10554

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27705 AN: 67932

Other (OTH) AF: 0.398 AC: 835 AN: 2098

Alfa AF: 0.392 Hom.: 1468

Bravo AF: 0.355

Asia WGS AF: 0.322 AC: 1119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.49
DANN	Benign	0.52
PhyloP100		-0.099
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: rs3771076; hg19: chr2-188277123;