rs2063505

Variant names:

• chr2-187423438-A-G
• rs2063505
• NM_005795.6:c.-293+24601T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-187423438-A-G
• chr2-187423438-A-T

Variant summary

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

The NM_005795.6(CALCRL):​c.-293+24601T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,556 control chromosomes in the GnomAD database, including 6,631 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 0.28 (6631 hom., cov: 31)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.-293+24601T>C		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.-293+24601T>C		intron_variant	Intron 1 of 14	1	NM_005795.6	ENSP00000376177.3

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42022 AN: 151442 Hom.: 6625 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.277 AC: 42018 AN: 151556 Hom.: 6631 Cov.: 31 AF XY: 0.273 AC XY: 20243 AN XY: 74062

African (AFR) AF: 0.139 AC: 5741 AN: 41434

American (AMR) AF: 0.312 AC: 4741 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1289 AN: 3458

East Asian (EAS) AF: 0.197 AC: 1015 AN: 5146

South Asian (SAS) AF: 0.337 AC: 1621 AN: 4812

European-Finnish (FIN) AF: 0.254 AC: 2661 AN: 10488

Middle Eastern (MID) AF: 0.324 AC: 94 AN: 290

European-Non Finnish (NFE) AF: 0.353 AC: 23915 AN: 67708

Other (OTH) AF: 0.284 AC: 598 AN: 2106

Alfa AF: 0.329 Hom.: 5494

Bravo AF: 0.279

Asia WGS AF: 0.265 AC: 922 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.84
PhyloP100		2.7
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: rs2063505; hg19: chr2-188288165;