chr2-187342518-A-G

Variant names:

• chr2-187342518-A-G
• rs1528233
• NM_005795.6:c.*3666T>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.*3666T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,324 control chromosomes in the GnomAD database, including 28,296 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 (28296 hom., cov: 30)
• Consequence: CALCRL NM_005795.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005795.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCRL	NM_005795.6	MANE Select	c.*3666T>C		3_prime_UTR	Exon 15 of 15	NP_005786.1	Q16602
	CALCRL	NM_001271751.2		c.*3666T>C		3_prime_UTR	Exon 14 of 14	NP_001258680.1	Q16602
	CALCRL	NM_001369434.1		c.*3666T>C		3_prime_UTR	Exon 16 of 16	NP_001356363.1	Q16602

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCRL	ENST00000392370.8	TSL:1 MANE Select	c.*3666T>C		3_prime_UTR	Exon 15 of 15	ENSP00000376177.3	Q16602
	CALCRL	ENST00000897822.1		c.*3666T>C		3_prime_UTR	Exon 14 of 14	ENSP00000567881.1
	CALCRL	ENST00000969621.1		c.*3666T>C		3_prime_UTR	Exon 16 of 16	ENSP00000639680.1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90356 AN: 151206 Hom.: 28283 Cov.: 30

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.597 AC: 90411 AN: 151324 Hom.: 28296 Cov.: 30 AF XY: 0.603 AC XY: 44581 AN XY: 73962

African (AFR) AF: 0.407 AC: 16852 AN: 41374

American (AMR) AF: 0.691 AC: 10484 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2029 AN: 3462

East Asian (EAS) AF: 0.864 AC: 4467 AN: 5168

South Asian (SAS) AF: 0.639 AC: 3083 AN: 4822

European-Finnish (FIN) AF: 0.690 AC: 7271 AN: 10540

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.657 AC: 44319 AN: 67488

Other (OTH) AF: 0.571 AC: 1201 AN: 2102

Alfa AF: 0.630 Hom.: 30816

Bravo AF: 0.592

Asia WGS AF: 0.700 AC: 2426 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.54
PhyloP100		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1528233; hg19: chr2-188207245;