2-187373374-T-C

Variant names:

• chr2-187373374-T-C
• rs6759535
• NM_005795.6:c.500+5566A>G

Variant summary

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

The NM_005795.6(CALCRL):​c.500+5566A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,004 control chromosomes in the GnomAD database, including 22,082 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 0.53 (22082 hom., cov: 33)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.630

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.500+5566A>G		intron_variant	Intron 8 of 14	ENST00000392370.8	NP_005786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCRL	ENST00000392370.8	c.500+5566A>G		intron_variant	Intron 8 of 14	1	NM_005795.6	ENSP00000376177.3

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80495 AN: 151886 Hom.: 22071 Cov.: 33

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.517

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

GnomAD4 genome AF: 0.530 AC: 80532 AN: 152004 Hom.: 22082 Cov.: 33 AF XY: 0.535 AC XY: 39752 AN XY: 74312

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.512

Alfa AF: 0.549 Hom.: 4050

Bravo AF: 0.534

Asia WGS AF: 0.592 AC: 2056 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
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: rs6759535; hg19: chr2-188238101;