2-187365606-A-T

Variant names:

• chr2-187365606-A-T
• rs840617
• NM_005795.6:c.501-2104T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 = 0.837 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.501-2104T>A		intron	N/A	NP_005786.1	Q16602
	CALCRL	NM_001271751.2		c.501-2104T>A		intron	N/A	NP_001258680.1	Q16602
	CALCRL	NM_001369434.1		c.501-2104T>A		intron	N/A	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.501-2104T>A		intron	N/A	ENSP00000376177.3	Q16602
	CALCRL	ENST00000409998.5	TSL:5	c.501-2104T>A		intron	N/A	ENSP00000386972.1	Q16602
	CALCRL	ENST00000410068.5	TSL:2	c.501-2104T>A		intron	N/A	ENSP00000387190.1	Q16602

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

African (AFR) AF: 0.721 AC: 29903 AN: 41458

American (AMR) AF: 0.788 AC: 12032 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3044 AN: 3472

East Asian (EAS) AF: 0.744 AC: 3841 AN: 5166

South Asian (SAS) AF: 0.787 AC: 3791 AN: 4818

European-Finnish (FIN) AF: 0.849 AC: 9001 AN: 10604

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57290 AN: 68002

Other (OTH) AF: 0.814 AC: 1720 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.5
DANN	Benign	0.35
PhyloP100		0.68
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: rs840617; hg19: chr2-188230333;