Variant 15-57438393-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032866.5(CGNL1):c.394C>G(p.Arg132Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,614,034 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

CGNL1
NM_032866.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.489

Variant links:

Genes affected

CGNL1 (HGNC:25931): (cingulin like 1) This gene encodes a member of the cingulin family. The encoded protein localizes to both adherens and tight cell-cell junctions and mediates junction assembly and maintenance by regulating the activity of the small GTPases RhoA and Rac1. Heterozygous chromosomal rearrangements resulting in association of the promoter for this gene with the aromatase gene are a cause of aromatase excess syndrome. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Nov 2011]

CGNL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012991995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CGNL1	NM_032866.5 linkuse as main transcript	c.394C>G	p.Arg132Gly	missense_variant	2/19	ENST00000281282.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CGNL1	ENST00000281282.6 linkuse as main transcript	c.394C>G	p.Arg132Gly	missense_variant	2/19	1	NM_032866.5	P1	Q0VF96-1

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000191

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000179

AC:

AN:

251160

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000434

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:

0.000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000352

AC:

515

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

241

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000514

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:

0.000425

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000177

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.0000497

Hom.:

Bravo

AF:

0.000249

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 08, 2023

The c.394C>G (p.R132G) alteration is located in exon 2 (coding exon 1) of the CGNL1 gene. This alteration results from a C to G substitution at nucleotide position 394, causing the arginine (R) at amino acid position 132 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.73

Cadd

Benign

1.4

Dann

Benign

0.84

DEOGEN2

Benign

0.0071

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.44

M_CAP

Benign

0.0029

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.92

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.39

REVEL

Benign

0.021

Sift

Benign

0.38

Sift4G

Benign

0.49

Polyphen

0.0

Vest4

0.19

MVP

0.12

MPC

0.019

ClinPred

0.0041

GERP RS

0.87

Varity_R

0.046

gMVP

0.18

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