Variant rs12112301 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000222792.11(CHN2):c.290+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 1,572,172 control chromosomes in the GnomAD database, including 6,458 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.093 ( 730 hom., cov: 32)

Exomes 𝑓: 0.087 ( 5728 hom. )

Consequence

CHN2
ENST00000222792.11 splice_region, intron

Scores

Splicing: ADA: 0.0002304

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.997

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 (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHN2	NM_004067.4 linkuse as main transcript	c.290+7C>T		splice_region_variant, intron_variant		ENST00000222792.11	NP_004058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11 linkuse as main transcript	c.290+7C>T		splice_region_variant, intron_variant		1	NM_004067.4	ENSP00000222792	P1	P52757-1

Frequencies

GnomAD3 genomes

AF:

0.0926

AC:

14088

AN:

152072

Hom.:

727

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0991

Gnomad AMI

AF:

0.0736

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.0734

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0811

Gnomad OTH

AF:

0.0953

GnomAD3 exomes

AF:

0.0968

AC:

24160

AN:

249588

Hom.:

1368

AF XY:

0.0968

AC XY:

13067

AN XY:

134956

show subpopulations

Gnomad AFR exome

AF:

0.0953

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.0549

Gnomad EAS exome

AF:

0.170

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.0762

Gnomad NFE exome

AF:

0.0822

Gnomad OTH exome

AF:

0.0915

GnomAD4 exome

AF:

0.0867

AC:

123074

AN:

1419982

Hom.:

5728

Cov.:

AF XY:

0.0878

AC XY:

62264

AN XY:

709258

show subpopulations

Gnomad4 AFR exome

AF:

0.0991

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.0548

Gnomad4 EAS exome

AF:

0.153

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.0778

Gnomad4 NFE exome

AF:

0.0812

Gnomad4 OTH exome

AF:

0.0874

GnomAD4 genome

AF:

0.0927

AC:

14106

AN:

152190

Hom.:

730

Cov.:

AF XY:

0.0940

AC XY:

6992

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0993

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.0510

Gnomad4 EAS

AF:

0.174

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.0734

Gnomad4 NFE

AF:

0.0811

Gnomad4 OTH

AF:

0.0948

Alfa

AF:

0.0818

Hom.:

1026

Bravo

AF:

0.0947

Asia WGS

AF:

0.147

AC:

509

AN:

3478

EpiCase

AF:

0.0772

EpiControl

AF:

0.0784

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.84

DANN

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00023

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.040

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