Menu
GeneBe

2-187360602-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_005795.6(CALCRL):c.777C>T(p.Gly259=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000392 in 1,608,984 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

CALCRL
NM_005795.6 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.108
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-AS1 (HGNC:55863): (CALCRL and TFPI antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-187360602-G-A is Benign according to our data. Variant chr2-187360602-G-A is described in ClinVar as [Benign]. Clinvar id is 789709.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.108 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CALCRLNM_005795.6 linkuse as main transcriptc.777C>T p.Gly259= synonymous_variant 10/15 ENST00000392370.8
CALCRL-AS1XR_007087504.1 linkuse as main transcriptn.3420-138904G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CALCRLENST00000392370.8 linkuse as main transcriptc.777C>T p.Gly259= synonymous_variant 10/151 NM_005795.6 P1
CALCRL-AS1ENST00000412276.6 linkuse as main transcriptn.190-138904G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00190
AC:
289
AN:
151890
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00664
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000657
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000442
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000514
AC:
127
AN:
247106
Hom.:
0
AF XY:
0.000404
AC XY:
54
AN XY:
133502
show subpopulations
Gnomad AFR exome
AF:
0.00674
Gnomad AMR exome
AF:
0.000414
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.000334
GnomAD4 exome
AF:
0.000233
AC:
339
AN:
1456976
Hom.:
0
Cov.:
31
AF XY:
0.000190
AC XY:
138
AN XY:
724602
show subpopulations
Gnomad4 AFR exome
AF:
0.00794
Gnomad4 AMR exome
AF:
0.000363
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000451
Gnomad4 OTH exome
AF:
0.000864
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00192
AC:
292
AN:
152008
Hom.:
1
Cov.:
32
AF XY:
0.00205
AC XY:
152
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.00670
Gnomad4 AMR
AF:
0.000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000816
Hom.:
0
Bravo
AF:
0.00223
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
10
Dann
Benign
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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.

Other links and lift over

dbSNP: rs111617832; hg19: chr2-188225329; API