rs2882203

Variant names:

• chr2-187417603-T-A
• rs2882203
• NM_005795.6:c.-292-29847A>T

Your query was ambiguous. Multiple possible variants found:

• chr2-187417603-T-A
• chr2-187417603-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005795.6(CALCRL):​c.-292-29847A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,842 control chromosomes in the GnomAD database, including 11,036 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 0.38 (11036 hom., cov: 32)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.-292-29847A>T		intron_variant	Intron 1 of 14	ENST00000392370.8	NP_005786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCRL	ENST00000392370.8	c.-292-29847A>T		intron_variant	Intron 1 of 14	1	NM_005795.6	ENSP00000376177.3

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57336 AN: 151724 Hom.: 11016 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.378 AC: 57399 AN: 151842 Hom.: 11036 Cov.: 32 AF XY: 0.374 AC XY: 27787 AN XY: 74220

African (AFR) AF: 0.372 AC: 15420 AN: 41430

American (AMR) AF: 0.313 AC: 4782 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1373 AN: 3468

East Asian (EAS) AF: 0.152 AC: 790 AN: 5184

South Asian (SAS) AF: 0.432 AC: 2082 AN: 4814

European-Finnish (FIN) AF: 0.366 AC: 3846 AN: 10498

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.408 AC: 27695 AN: 67872

Other (OTH) AF: 0.407 AC: 858 AN: 2106

Alfa AF: 0.259 Hom.: 640

Bravo AF: 0.367

Asia WGS AF: 0.320 AC: 1092 AN: 3418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.65
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2882203; hg19: chr2-188282330;