Genetic Variant CHN2:p.Asn423Asn (chr7-29512597-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004067.4(CHN2):c.1269T>C(p.Asn423Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 1,613,070 control chromosomes in the GnomAD database, including 11,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.16 ( 4239 hom., cov: 32)

Exomes 𝑓: 0.044 ( 7095 hom. )

Consequence

CHN2
NM_004067.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.111

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:

PRR15-DT (HGNC:55866): (PRR15 divergent transcript)

PRR15-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 7-29512597-T-C is Benign according to our data. Variant chr7-29512597-T-C is described in ClinVar as [Benign]. Clinvar id is 3060363.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.111 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN2	NM_004067.4 link	c.1269T>C	p.Asn423Asn	synonymous_variant	Exon 13 of 13	ENST00000222792.11	NP_004058.1	P52757-1A0A2X0TVW3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11 link	c.1269T>C	p.Asn423Asn	synonymous_variant	Exon 13 of 13	1	NM_004067.4	ENSP00000222792.7		P52757-1

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24009

AN:

152004

Hom.:

4205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.0773

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.104

AC:

26001

AN:

250316

Hom.:

3157

AF XY:

0.0938

AC XY:

12694

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.429

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.0165

Gnomad EAS exome

AF:

0.289

Gnomad SAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.0770

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.0654

GnomAD4 exome

AF:

0.0439

AC:

64155

AN:

1460948

Hom.:

7095

Cov.:

AF XY:

0.0451

AC XY:

32767

AN XY:

726722

show subpopulations

Gnomad4 AFR exome

AF:

0.441

Gnomad4 AMR exome

AF:

0.166

Gnomad4 ASJ exome

AF:

0.0180

Gnomad4 EAS exome

AF:

0.290

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.0735

Gnomad4 NFE exome

AF:

0.00902

Gnomad4 OTH exome

AF:

0.0710

GnomAD4 genome

AF:

0.158

AC:

24104

AN:

152122

Hom.:

4239

Cov.:

AF XY:

0.163

AC XY:

12125

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.427

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.0185

Gnomad4 EAS

AF:

0.293

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.0773

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.0533

Hom.:

1450

Bravo

AF:

0.174

Asia WGS

AF:

0.232

AC:

809

AN:

3478

EpiCase

AF:

0.0125

EpiControl

AF:

0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CHN2-related disorder

Benign:1

Jul 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.56

CADD

Benign

2.7

DANN

Benign

0.74

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