2-187365606-A-T

Variant summary

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

The NM_005795.6(CALCRL):c.501-2104T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,118 control chromosomes in the GnomAD database, including 49,030 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 0.80 (49030 hom., cov: 32)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CALCRL	NM_005795.6	c.501-2104T>A		intron_variant		ENST00000392370.8
CALCRL-AS1	XR_007087504.1	n.3420-133900A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCRL	ENST00000392370.8	c.501-2104T>A		intron_variant		1	NM_005795.6	P1
CALCRL-AS1	ENST00000412276.6	n.190-133900A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121610 AN: 152000 Hom.: 49001 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.800 AC: 121683 AN: 152118 Hom.: 49030 Cov.: 32 AF XY: 0.799 AC XY: 59401 AN XY: 74360

Gnomad4 AFR AF: 0.721

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.877

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.842

Gnomad4 OTH AF: 0.814

Alfa AF: 0.824 Hom.: 6437

Bravo AF: 0.794

Asia WGS AF: 0.774 AC: 2688 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.5
Dann	Benign	0.35

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: rs840617; hg19: chr2-188230333;