rs12104503

Positions:

• chr2-187432406-T-G

Variant summary

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

The NM_005795.6(CALCRL):​c.-293+15633A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,866 control chromosomes in the GnomAD database, including 13,972 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 0.41 (13972 hom., cov: 32)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.-293+15633A>C		intron_variant		ENST00000392370.8	NP_005786.1
CALCRL-AS1	XR_007087504.1	n.3420-67100T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCRL	ENST00000392370.8	c.-293+15633A>C		intron_variant		1	NM_005795.6	ENSP00000376177	P1
CALCRL-AS1	ENST00000412276.6	n.190-67100T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62598 AN: 151750 Hom.: 13940 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.413 AC: 62690 AN: 151866 Hom.: 13972 Cov.: 32 AF XY: 0.409 AC XY: 30347 AN XY: 74230

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.419

Alfa AF: 0.374 Hom.: 21105

Bravo AF: 0.413

Asia WGS AF: 0.328 AC: 1137 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.16
DANN	Benign	0.39

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: rs12104503; hg19: chr2-188297133;