chr2-187397603-A-G

Variant names:

• chr2-187397603-A-G
• rs698574
• NM_005795.6:c.-292-9847T>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.-292-9847T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 151,752 control chromosomes in the GnomAD database, including 138 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 0.023 (138 hom., cov: 32)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 0 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.-292-9847T>C		intron_variant	Intron 1 of 14	ENST00000392370.8	NP_005786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCRL	ENST00000392370.8	c.-292-9847T>C		intron_variant	Intron 1 of 14	1	NM_005795.6	ENSP00000376177.3

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3509 AN: 151632 Hom.: 138 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000487

Gnomad OTH AF: 0.0163

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

GnomAD4 genome AF: 0.0231 AC: 3512 AN: 151752 Hom.: 138 Cov.: 32 AF XY: 0.0223 AC XY: 1658 AN XY: 74196

African (AFR) AF: 0.0798 AC: 3310 AN: 41468

American (AMR) AF: 0.00883 AC: 134 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000487 AC: 33 AN: 67718

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

Alfa AF: 0.0215 Hom.: 17

Bravo AF: 0.0273

Asia WGS AF: 0.00347 AC: 13 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.39
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism

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: rs698574; hg19: chr2-188262330;