dbSNP rs2023908: CHN2:c.50-66715C>A (chr7-29287910-C-A) – 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.50-66715C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,022 control chromosomes in the GnomAD database, including 42,337 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 0.74 ( 42337 hom., cov: 32)

Consequence

CHN2
NM_004067.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.757

Publications

5 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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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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 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.50-66715C>A	intron	N/A	NP_004058.1	P52757-1
CHN2	NM_001293070.2		c.50-5015C>A	intron	N/A	NP_001279999.1	B7Z1V0
CHN2	NM_001293072.2		c.5-66715C>A	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.50-66715C>A	intron	N/A	ENSP00000222792.7	P52757-1
CHN2	ENST00000706161.1		c.50-5015C>A	intron	N/A	ENSP00000516239.1	A0A994J7L4
CHN2	ENST00000409350.6	TSL:4	c.50-5015C>A	intron	N/A	ENSP00000386968.2	B7Z1V0

Frequencies

GnomAD3 genomes

AF:

0.744

AC:

112972

AN:

151904

Hom.:

42316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.657

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.735

Gnomad ASJ

AF:

0.838

Gnomad EAS

AF:

0.785

Gnomad SAS

AF:

0.680

Gnomad FIN

AF:

0.809

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.784

Gnomad OTH

AF:

0.745

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

GnomAD4 genome

AF:

0.744

AC:

113044

AN:

152022

Hom.:

42337

Cov.:

AF XY:

0.744

AC XY:

55269

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.657

AC:

27205

AN:

41426

American (AMR)

AF:

0.736

AC:

11233

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.838

AC:

2907

AN:

3470

East Asian (EAS)

AF:

0.784

AC:

4052

AN:

5166

South Asian (SAS)

AF:

0.681

AC:

3275

AN:

4812

European-Finnish (FIN)

AF:

0.809

AC:

8543

AN:

10558

Middle Eastern (MID)

AF:

0.684

AC:

201

AN:

294

European-Non Finnish (NFE)

AF:

0.784

AC:

53340

AN:

68004

Other (OTH)

AF:

0.748

AC:

1576

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1441

2881

4322

5762

7203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.771

Hom.:

138326

Bravo

AF:

0.738

Asia WGS

AF:

0.729

AC:

2533

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.8

(source)

DANN

Benign

0.60

PhyloP100

0.76

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

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