2-187393258-C-T

Position:

• chr2-187393258-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000392370.8(CALCRL):​c.-292-5502G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 151,842 control chromosomes in the GnomAD database, including 37,385 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 0.70 (37385 hom., cov: 31)
• Consequence: CALCRL ENST00000392370.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.-292-5502G>A		intron_variant		ENST00000392370.8	NP_005786.1
CALCRL-AS1	XR_007087504.1	n.3420-106248C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCRL	ENST00000392370.8	c.-292-5502G>A		intron_variant		1	NM_005795.6	ENSP00000376177	P1
CALCRL-AS1	ENST00000412276.6	n.190-106248C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106172 AN: 151724 Hom.: 37352 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.700 AC: 106254 AN: 151842 Hom.: 37385 Cov.: 31 AF XY: 0.702 AC XY: 52110 AN XY: 74202

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.669

Alfa AF: 0.674 Hom.: 7041

Bravo AF: 0.708

Asia WGS AF: 0.732 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs1398061; hg19: chr2-188257985;