2-187352080-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005795.6(CALCRL):c.1128+34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,593,056 control chromosomes in the GnomAD database, including 590,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.87 (57464 hom., cov: 31)
  • Exomes 𝑓: 0.86 (533185 hom.)
• Consequence: CALCRL NM_005795.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.227

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-187352080-T-C is Benign according to our data. Variant chr2-187352080-T-C is described in ClinVar as [Benign]. Clinvar id is 1192647.Status of the report is criteria_provided_single_submitter, 1 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	UniProt
CALCRL	NM_005795.6	c.1128+34A>G		intron_variant		ENST00000392370.8
CALCRL-AS1	XR_007087504.1	n.3420-147426T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CALCRL	ENST00000392370.8	c.1128+34A>G		intron_variant		1	NM_005795.6	P1
CALCRL-AS1	ENST00000412276.6	n.190-147426T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.869 AC: 131662 AN: 151564 Hom.: 57410 Cov.: 31

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.871

GnomAD3 exomes AF: 0.845 AC: 210952 AN: 249514 Hom.: 89540 AF XY: 0.846 AC XY: 114147 AN XY: 134864

Gnomad AFR exome AF: 0.906

Gnomad AMR exome AF: 0.793

Gnomad ASJ exome AF: 0.904

Gnomad EAS exome AF: 0.741

Gnomad SAS exome AF: 0.807

Gnomad FIN exome AF: 0.886

Gnomad NFE exome AF: 0.867

Gnomad OTH exome AF: 0.855

GnomAD4 exome AF: 0.859 AC: 1238603 AN: 1441374 Hom.: 533185 Cov.: 26 AF XY: 0.858 AC XY: 616247 AN XY: 718290

Gnomad4 AFR exome AF: 0.913

Gnomad4 AMR exome AF: 0.794

Gnomad4 ASJ exome AF: 0.906

Gnomad4 EAS exome AF: 0.753

Gnomad4 SAS exome AF: 0.812

Gnomad4 FIN exome AF: 0.886

Gnomad4 NFE exome AF: 0.865

Gnomad4 OTH exome AF: 0.865

GnomAD4 genome AF: 0.869 AC: 131771 AN: 151682 Hom.: 57464 Cov.: 31 AF XY: 0.867 AC XY: 64241 AN XY: 74124

Gnomad4 AFR AF: 0.909

Gnomad4 AMR AF: 0.817

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.871

Alfa AF: 0.878 Hom.: 11875

Bravo AF: 0.866

Asia WGS AF: 0.789 AC: 2743 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lymphatic malformation 8 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.0
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs858745; hg19: chr2-188216807; COSMIC: COSV66474479;