rs9288141

Variant names:

• chr2-187394893-A-G
• rs9288141
• NM_005795.6:c.-292-7137T>C

Variant summary

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

The NM_005795.6(CALCRL):​c.-292-7137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 152,096 control chromosomes in the GnomAD database, including 586 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 0.076 (586 hom., cov: 32)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.-292-7137T>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.-292-7137T>C		intron_variant	Intron 1 of 14	1	NM_005795.6	ENSP00000376177.3

Frequencies

GnomAD3 genomes AF: 0.0756 AC: 11487 AN: 151978 Hom.: 586 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0373

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0368

Gnomad FIN AF: 0.0696

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0440

Gnomad OTH AF: 0.0744

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

GnomAD4 genome AF: 0.0755 AC: 11488 AN: 152096 Hom.: 586 Cov.: 32 AF XY: 0.0779 AC XY: 5795 AN XY: 74360

African (AFR) AF: 0.101 AC: 4202 AN: 41512

American (AMR) AF: 0.140 AC: 2131 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0373 AC: 129 AN: 3462

East Asian (EAS) AF: 0.178 AC: 917 AN: 5154

South Asian (SAS) AF: 0.0364 AC: 176 AN: 4830

European-Finnish (FIN) AF: 0.0696 AC: 738 AN: 10604

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0440 AC: 2991 AN: 67984

Other (OTH) AF: 0.0736 AC: 155 AN: 2106

Alfa AF: 0.0617 Hom.: 156

Bravo AF: 0.0847

Asia WGS AF: 0.100 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.51
DANN	Benign	0.25
PhyloP100		-1.4
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: rs9288141; hg19: chr2-188259620;