2-187342518-A-G

Variant summary

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

The NM_005795.6(CALCRL):c.*3666T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,324 control chromosomes in the GnomAD database, including 28,296 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 0.60 (28296 hom., cov: 30)
• Consequence: CALCRL NM_005795.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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 (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCRL	NM_005795.6	c.*3666T>C		3_prime_UTR_variant	15/15	ENST00000392370.8
CALCRL-AS1	XR_007087504.1	n.3419+150640A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCRL	ENST00000392370.8	c.*3666T>C		3_prime_UTR_variant	15/15	1	NM_005795.6	P1
CALCRL-AS1	ENST00000412276.6	n.189+150587A>G		intron_variant, non_coding_transcript_variant		5
CALCRL-AS1	ENST00000453517.5	n.243+150587A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90356 AN: 151206 Hom.: 28283 Cov.: 30

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.597 AC: 90411 AN: 151324 Hom.: 28296 Cov.: 30 AF XY: 0.603 AC XY: 44581 AN XY: 73962

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.571

Alfa AF: 0.633 Hom.: 26600

Bravo AF: 0.592

Asia WGS AF: 0.700 AC: 2426 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.0
Dann	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1528233; hg19: chr2-188207245;