rs13411274

Variant names:

• chr2-187371273-A-C
• rs13411274
• NM_005795.6:c.500+7667T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-187371273-A-C
• chr2-187371273-A-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.500+7667T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,562 control chromosomes in the GnomAD database, including 6,925 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 0.30 (6925 hom., cov: 31)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.334 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.500+7667T>G		intron	N/A	NP_005786.1	Q16602
	CALCRL	NM_001271751.2		c.500+7667T>G		intron	N/A	NP_001258680.1	Q16602
	CALCRL	NM_001369434.1		c.500+7667T>G		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.500+7667T>G		intron	N/A	ENSP00000376177.3	Q16602
	CALCRL	ENST00000409998.5	TSL:5	c.500+7667T>G		intron	N/A	ENSP00000386972.1	Q16602
	CALCRL	ENST00000410068.5	TSL:2	c.500+7667T>G		intron	N/A	ENSP00000387190.1	Q16602

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44897 AN: 151444 Hom.: 6921 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.296 AC: 44921 AN: 151562 Hom.: 6925 Cov.: 31 AF XY: 0.294 AC XY: 21793 AN XY: 74080

African (AFR) AF: 0.235 AC: 9698 AN: 41312

American (AMR) AF: 0.267 AC: 4058 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1336 AN: 3456

East Asian (EAS) AF: 0.176 AC: 903 AN: 5120

South Asian (SAS) AF: 0.347 AC: 1663 AN: 4786

European-Finnish (FIN) AF: 0.308 AC: 3228 AN: 10496

Middle Eastern (MID) AF: 0.414 AC: 120 AN: 290

European-Non Finnish (NFE) AF: 0.336 AC: 22838 AN: 67874

Other (OTH) AF: 0.340 AC: 715 AN: 2102

Alfa AF: 0.322 Hom.: 22182

Bravo AF: 0.288

Asia WGS AF: 0.283 AC: 981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.63
PhyloP100		1.1
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: rs13411274; hg19: chr2-188236000;