2-187394177-C-T

Variant names:

• chr2-187394177-C-T
• rs1157699
• NM_005795.6:c.-292-6421G>A

Variant summary

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

The NM_005795.6(CALCRL):​c.-292-6421G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,820 control chromosomes in the GnomAD database, including 6,152 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 0.27 (6152 hom., cov: 32)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.-292-6421G>A		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.-292-6421G>A		intron_variant	Intron 1 of 14	1	NM_005795.6	ENSP00000376177.3

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40682 AN: 151702 Hom.: 6146 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.268 AC: 40685 AN: 151820 Hom.: 6152 Cov.: 32 AF XY: 0.265 AC XY: 19664 AN XY: 74190

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.273

Alfa AF: 0.318 Hom.: 15650

Bravo AF: 0.271

Asia WGS AF: 0.266 AC: 930 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	0.39
DANN	Benign	0.59

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: rs1157699; hg19: chr2-188258904;