rs698576

Variant names:

• chr2-187387109-G-A
• rs698576
• NM_005795.6:c.-37+220C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-187387109-G-A
• chr2-187387109-G-C
• chr2-187387109-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005795.6(CALCRL):​c.-37+220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 152,192 control chromosomes in the GnomAD database, including 152 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 0.024 (152 hom., cov: 32)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALCRL	NM_005795.6	c.-37+220C>T		intron_variant	Intron 3 of 14	ENST00000392370.8	NP_005786.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALCRL	ENST00000392370.8	c.-37+220C>T		intron_variant	Intron 3 of 14	1	NM_005795.6	ENSP00000376177.3

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3674 AN: 152074 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00944

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: 0.000515

Gnomad OTH AF: 0.0163

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

GnomAD4 genome AF: 0.0241 AC: 3675 AN: 152192 Hom.: 152 Cov.: 32 AF XY: 0.0234 AC XY: 1738 AN XY: 74412

African (AFR) AF: 0.0834 AC: 3461 AN: 41512

American (AMR) AF: 0.00943 AC: 144 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68014

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

Alfa AF: 0.00911 Hom.: 5

Bravo AF: 0.0283

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.62
DANN	Benign	0.70
PhyloP100		-0.37
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

Publications

LitVar

Other links and lift over

dbSNP: rs698576; hg19: chr2-188251836;