Variant chr2-187359330-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005795.6(CALCRL):c.782-58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 1,243,314 control chromosomes in the GnomAD database, including 463,646 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 57602 hom., cov: 31)

Exomes 𝑓: 0.86 ( 406044 hom. )

Consequence

CALCRL
NM_005795.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00500

Variant links:

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 links:

CALCRL-AS1 (HGNC:55863): (CALCRL and TFPI antisense RNA 1)

CALCRL-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-187359330-A-G is Benign according to our data. Variant chr2-187359330-A-G is described in ClinVar as [Benign]. Clinvar id is 1192648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALCRL	NM_005795.6 linkuse as main transcript	c.782-58T>C		intron_variant		ENST00000392370.8	NP_005786.1
CALCRL-AS1	XR_007087504.1 linkuse as main transcript	n.3420-140176A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALCRL	ENST00000392370.8 linkuse as main transcript	c.782-58T>C		intron_variant		1	NM_005795.6	ENSP00000376177	P1
CALCRL-AS1	ENST00000412276.6 linkuse as main transcript	n.190-140176A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.869

AC:

131928

AN:

151798

Hom.:

57548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.909

Gnomad AMI

AF:

0.889

Gnomad AMR

AF:

0.818

Gnomad ASJ

AF:

0.912

Gnomad EAS

AF:

0.752

Gnomad SAS

AF:

0.802

Gnomad FIN

AF:

0.884

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.865

Gnomad OTH

AF:

0.870

GnomAD4 exome

AF:

0.862

AC:

940807

AN:

1091398

Hom.:

406044

AF XY:

0.860

AC XY:

467543

AN XY:

543446

show subpopulations

Gnomad4 AFR exome

AF:

0.915

Gnomad4 AMR exome

AF:

0.804

Gnomad4 ASJ exome

AF:

0.907

Gnomad4 EAS exome

AF:

0.756

Gnomad4 SAS exome

AF:

0.822

Gnomad4 FIN exome

AF:

0.885

Gnomad4 NFE exome

AF:

0.866

Gnomad4 OTH exome

AF:

0.868

GnomAD4 genome

AF:

0.869

AC:

132037

AN:

151916

Hom.:

57602

Cov.:

AF XY:

0.867

AC XY:

64405

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.909

Gnomad4 AMR

AF:

0.818

Gnomad4 ASJ

AF:

0.912

Gnomad4 EAS

AF:

0.752

Gnomad4 SAS

AF:

0.801

Gnomad4 FIN

AF:

0.884

Gnomad4 NFE

AF:

0.865

Gnomad4 OTH

AF:

0.871

Alfa

AF:

0.872

Hom.:

9351

Bravo

AF:

0.867

Asia WGS

AF:

0.794

AC:

2745

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Lymphatic malformation 8

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.5

DANN

Benign

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over