Variant 7-29146736-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001398427.1(CHN2):c.-511T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00076 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHN2
NM_001398427.1 5_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.82

Variant links:

Genes affected

CHN2 (HGNC:1944): (chimerin 2) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that contains a phorbol-ester/diacylglycerol (DAG)-type zinc finger, a Rho-GAP domain, and an SH2 domain. The encoded protein translocates from the cytosol to the Golgi apparatus membrane upon binding by diacylglycerol (DAG). Activity of this protein is important in cell proliferation and migration, and expression changes in this gene have been detected in cancers. A mutation in this gene has also been associated with schizophrenia in men. Alternative transcript splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, May 2014]

CHN2 links:

CPVL (HGNC:14399): (carboxypeptidase vitellogenic like) The protein encoded by this gene is a carboxypeptidase and bears strong sequence similarity to serine carboxypeptidases. Carboxypeptidases are a large class of proteases that act to cleave a single amino acid from the carboxy termini of proteins or peptides. The exact function of this protein, however, has not been determined. [provided by RefSeq, Jan 2017]

CPVL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 7-29146736-T-G is Benign according to our data. Variant chr7-29146736-T-G is described in ClinVar as [Benign]. Clinvar id is 3035343.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
CHN2	NM_001398427.1 linkuse as main transcript	c.-511T>G	5_prime_UTR_variant	1/14	NP_001385356.1
CHN2	XM_011515105.3 linkuse as main transcript	c.-589T>G	5_prime_UTR_variant	1/16	XP_011513407.2
CHN2	XM_011515106.3 linkuse as main transcript	c.-550T>G	5_prime_UTR_variant	1/15	XP_011513408.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	Appris
CPVL	ENST00000409850.5 linkuse as main transcript	c.-10-25665A>C	intron_variant	2	ENSP00000387164	P1
CPVL	ENST00000437527.1 linkuse as main transcript	c.-10-25665A>C	intron_variant	4	ENSP00000416555
CPVL	ENST00000449801.5 linkuse as main transcript	c.-10-25665A>C	intron_variant	4	ENSP00000413287

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151846

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.00

GnomAD3 exomes

AF:

0.00326

AC:

481

AN:

147412

Hom.:

AF XY:

0.00275

AC XY:

218

AN XY:

79366

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0197

Gnomad NFE exome

AF:

0.00275

Gnomad OTH exome

AF:

0.00304

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000755

AC:

1050

AN:

1390368

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

479

AN XY:

685870

show subpopulations

Gnomad4 AFR exome

AF:

0.000540

Gnomad4 AMR exome

AF:

0.0000561

Gnomad4 ASJ exome

AF:

0.000239

Gnomad4 EAS exome

AF:

0.000196

Gnomad4 SAS exome

AF:

0.000241

Gnomad4 FIN exome

AF:

0.000208

Gnomad4 NFE exome

AF:

0.000879

Gnomad4 OTH exome

AF:

0.000763

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000263

AC:

AN:

151846

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

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:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CHN2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.1

DANN

Benign

0.74

Splicing

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