Genetic Variant CHN2:p.His204Arg (chr7-29480313-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004067.4(CHN2):c.611A>G(p.His204Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0644 in 1,614,042 control chromosomes in the GnomAD database, including 4,602 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.094 ( 857 hom., cov: 32)

Exomes 𝑓: 0.061 ( 3745 hom. )

Consequence

CHN2
NM_004067.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.98

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00161618).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN2	NM_004067.4 link	c.611A>G	p.His204Arg	missense_variant	Exon 7 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.611A>G	p.His204Arg	missense_variant	Exon 7 of 13	1	NM_004067.4	ENSP00000222792.7		P52757-1

Frequencies

GnomAD3 genomes

AF:

0.0938

AC:

14269

AN:

152094

Hom.:

854

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.0779

Gnomad FIN

AF:

0.0624

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.0480

Gnomad OTH

AF:

0.0908

GnomAD3 exomes

AF:

0.0884

AC:

22228

AN:

251426

Hom.:

1287

AF XY:

0.0841

AC XY:

11434

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.149

Gnomad ASJ exome

AF:

0.115

Gnomad EAS exome

AF:

0.195

Gnomad SAS exome

AF:

0.0767

Gnomad FIN exome

AF:

0.0601

Gnomad NFE exome

AF:

0.0503

Gnomad OTH exome

AF:

0.0746

GnomAD4 exome

AF:

0.0613

AC:

89665

AN:

1461830

Hom.:

3745

Cov.:

AF XY:

0.0616

AC XY:

44781

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.208

Gnomad4 SAS exome

AF:

0.0759

Gnomad4 FIN exome

AF:

0.0575

Gnomad4 NFE exome

AF:

0.0471

Gnomad4 OTH exome

AF:

0.0707

GnomAD4 genome

AF:

0.0938

AC:

14281

AN:

152212

Hom.:

857

Cov.:

AF XY:

0.0965

AC XY:

7184

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.0770

Gnomad4 FIN

AF:

0.0624

Gnomad4 NFE

AF:

0.0480

Gnomad4 OTH

AF:

0.0899

Alfa

AF:

0.0624

Hom.:

843

Bravo

AF:

0.102

TwinsUK

AF:

0.0448

AC:

166

ALSPAC

AF:

0.0516

AC:

199

ESP6500AA

AF:

0.146

AC:

642

ESP6500EA

AF:

0.0493

AC:

424

ExAC

AF:

0.0853

AC:

10355

Asia WGS

AF:

0.140

AC:

487

AN:

3478

EpiCase

AF:

0.0533

EpiControl

AF:

0.0575

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.042

.;T;T;.;.;.;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

0.014

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D;D;D;D;D;D;D

MetaRNN

Benign

0.0016

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;N;.;.;.;.;.;.

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.81

.;N;.;.;N;N;.;N

REVEL

Benign

0.18

Sift

Benign

0.20

.;T;.;.;D;D;.;D

Sift4G

Benign

0.076

.;T;D;D;D;T;D;D

Polyphen

0.0010, 0.0, 0.019

.;B;.;.;B;.;B;B

Vest4

0.17, 0.12, 0.13, 0.17, 0.21, 0.22, 0.23

MPC

0.38

ClinPred

0.022

GERP RS

4.4

Varity_R

0.14

gMVP

0.32

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over