chr2-187381163-A-G

Variant names:

• chr2-187381163-A-G
• rs6706141
• NM_005795.6:c.185-376T>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.185-376T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,914 control chromosomes in the GnomAD database, including 6,807 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 0.29 (6807 hom., cov: 32)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCRL	NM_005795.6	MANE Select	c.185-376T>C		intron	N/A	NP_005786.1
	CALCRL	NM_001271751.2		c.185-376T>C		intron	N/A	NP_001258680.1
	CALCRL	NM_001369434.1		c.185-376T>C		intron	N/A	NP_001356363.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALCRL	ENST00000392370.8	TSL:1 MANE Select	c.185-376T>C		intron	N/A	ENSP00000376177.3
	CALCRL	ENST00000409998.5	TSL:5	c.185-376T>C		intron	N/A	ENSP00000386972.1
	CALCRL	ENST00000410068.5	TSL:2	c.185-376T>C		intron	N/A	ENSP00000387190.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44229 AN: 151798 Hom.: 6798 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.291 AC: 44248 AN: 151914 Hom.: 6807 Cov.: 32 AF XY: 0.288 AC XY: 21357 AN XY: 74278

African (AFR) AF: 0.223 AC: 9246 AN: 41458

American (AMR) AF: 0.320 AC: 4883 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1254 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1128 AN: 5176

South Asian (SAS) AF: 0.331 AC: 1588 AN: 4802

European-Finnish (FIN) AF: 0.242 AC: 2550 AN: 10530

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22607 AN: 67902

Other (OTH) AF: 0.288 AC: 608 AN: 2112

Alfa AF: 0.301 Hom.: 889

Bravo AF: 0.299

Asia WGS AF: 0.274 AC: 950 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.6
DANN	Benign	0.86
PhyloP100		0.20
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: rs6706141; hg19: chr2-188245890;