rs696092

chr2-187345487-G-Achr2-187345487-G-Cchr2-187345487-G-T

Variant summary

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

The NM_005795.6(CALCRL):c.*697C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,894 control chromosomes in the GnomAD database, including 28,477 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 (28381 hom., cov: 31)
  • Exomes 𝑓: 0.69 (96 hom.)
• Consequence: CALCRL NM_005795.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829

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=-0.79).
• 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.*697C>T		3_prime_UTR_variant	15/15	ENST00000392370.8
CALCRL-AS1	XR_007087504.1	n.3419+153609G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCRL	ENST00000392370.8	c.*697C>T		3_prime_UTR_variant	15/15	1	NM_005795.6	P1
CALCRL-AS1	ENST00000412276.6	n.189+153556G>A		intron_variant, non_coding_transcript_variant		5
CALCRL	ENST00000409998.5	c.*697C>T		3_prime_UTR_variant	16/16	5		P1
CALCRL-AS1	ENST00000453517.5	n.243+153556G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90576 AN: 151356 Hom.: 28368 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.576

GnomAD4 exome AF: 0.688 AC: 289 AN: 420 Hom.: 96 Cov.: 0 AF XY: 0.720 AC XY: 180 AN XY: 250

Gnomad4 FIN exome AF: 0.686

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.598 AC: 90631 AN: 151474 Hom.: 28381 Cov.: 31 AF XY: 0.604 AC XY: 44689 AN XY: 74016

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.864

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.571

Alfa AF: 0.633 Hom.: 27007

Bravo AF: 0.592

Asia WGS AF: 0.701 AC: 2440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.41
Dann	Benign	0.66

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: rs696092; hg19: chr2-188210214;