Genetic Variant CHN2:c.49+59856A>G (chr7-29254846-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004067.4(CHN2):c.49+59856A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,940 control chromosomes in the GnomAD database, including 35,129 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.66 ( 35129 hom., cov: 32)

Consequence

CHN2
NM_004067.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0190

Publications

6 publications found

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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new If you want to explore the variant's impact on the transcript NM_004067.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004067.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHN2	NM_004067.4	MANE Select	c.49+59856A>G	intron	N/A	NP_004058.1	P52757-1
CHN2	NM_001293070.2		c.50-38079A>G	intron	N/A	NP_001279999.1	B7Z1V0
CHN2	NM_001293072.2		c.4+56863A>G	intron	N/A	NP_001280001.1	B7Z1W9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHN2	ENST00000222792.11	TSL:1 MANE Select	c.49+59856A>G	intron	N/A	ENSP00000222792.7	P52757-1
CHN2	ENST00000706161.1		c.50-38079A>G	intron	N/A	ENSP00000516239.1	A0A994J7L4
CHN2	ENST00000409350.6	TSL:4	c.50-38079A>G	intron	N/A	ENSP00000386968.2	B7Z1V0

Frequencies

GnomAD3 genomes

AF:

0.662

AC:

100482

AN:

151822

Hom.:

35118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.428

Gnomad AMI

AF:

0.862

Gnomad AMR

AF:

0.783

Gnomad ASJ

AF:

0.718

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.597

Gnomad FIN

AF:

0.727

Gnomad MID

AF:

0.634

Gnomad NFE

AF:

0.751

Gnomad OTH

AF:

0.676

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.662

AC:

100525

AN:

151940

Hom.:

35129

Cov.:

AF XY:

0.661

AC XY:

49056

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.428

AC:

17707

AN:

41414

American (AMR)

AF:

0.783

AC:

11965

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.718

AC:

2492

AN:

3472

East Asian (EAS)

AF:

0.848

AC:

4356

AN:

5134

South Asian (SAS)

AF:

0.597

AC:

2874

AN:

4812

European-Finnish (FIN)

AF:

0.727

AC:

7663

AN:

10546

Middle Eastern (MID)

AF:

0.623

AC:

182

AN:

292

European-Non Finnish (NFE)

AF:

0.751

AC:

51073

AN:

67968

Other (OTH)

AF:

0.676

AC:

1427

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1594

3187

4781

6374

7968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.731

Hom.:

72127

Bravo

AF:

0.659

Asia WGS

AF:

0.696

AC:

2420

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.3

(source)

DANN

Benign

0.79

PhyloP100

0.019

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over