chr2-187439719-T-C

Variant names:

• chr2-187439719-T-C
• rs7591567
• NM_005795.6:c.-293+8320A>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.-293+8320A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,928 control chromosomes in the GnomAD database, including 9,364 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 0.34 (9364 hom., cov: 31)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 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.-293+8320A>G		intron	N/A	NP_005786.1
	CALCRL	NM_001271751.2		c.-128+8320A>G		intron	N/A	NP_001258680.1
	CALCRL	NM_001369434.1		c.-361+8320A>G		intron	N/A	NP_001356363.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCRL	ENST00000392370.8	TSL:1 MANE Select	c.-293+8320A>G		intron	N/A	ENSP00000376177.3
	CALCRL	ENST00000479784.1	TSL:1	n.108+8320A>G		intron	N/A
	CALCRL	ENST00000409998.5	TSL:5	c.-361+8320A>G		intron	N/A	ENSP00000386972.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51804 AN: 151810 Hom.: 9356 Cov.: 31

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.341 AC: 51848 AN: 151928 Hom.: 9364 Cov.: 31 AF XY: 0.337 AC XY: 24990 AN XY: 74246

African (AFR) AF: 0.455 AC: 18854 AN: 41404

American (AMR) AF: 0.272 AC: 4157 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3468

East Asian (EAS) AF: 0.135 AC: 696 AN: 5162

South Asian (SAS) AF: 0.289 AC: 1392 AN: 4820

European-Finnish (FIN) AF: 0.300 AC: 3174 AN: 10572

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21284 AN: 67930

Other (OTH) AF: 0.355 AC: 749 AN: 2108

Alfa AF: 0.266 Hom.: 944

Bravo AF: 0.343

Asia WGS AF: 0.260 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.39
PhyloP100		-0.63
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: rs7591567; hg19: chr2-188304446;