GeneBe

7-29507241-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6BP7

The NM_004067.4(CHN2):​c.1005C>T​(p.Ala335Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000202 in 1,607,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00090 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CHN2
NM_004067.4 synonymous

Scores

2

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.58
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]
PRR15-DT (HGNC:55866): (PRR15 divergent transcript)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (REVEL=0.111).
BP6
Variant 7-29507241-C-T is Benign according to our data. Variant chr7-29507241-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3048142.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-1.59 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHN2NM_004067.4 linkc.1005C>T p.Ala335Ala synonymous_variant Exon 11 of 13 ENST00000222792.11 NP_004058.1 P52757-1A0A2X0TVW3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHN2ENST00000222792.11 linkc.1005C>T p.Ala335Ala synonymous_variant Exon 11 of 13 1 NM_004067.4 ENSP00000222792.7 P52757-1

Frequencies

GnomAD3 genomes
AF:
0.000903
AC:
137
AN:
151752
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00303
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000263
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000736
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000368
AC:
90
AN:
244376
AF XY:
0.000280
show subpopulations
Gnomad AFR exome
AF:
0.00212
Gnomad AMR exome
AF:
0.00118
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000335
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000358
Gnomad OTH exome
AF:
0.000846
GnomAD4 exome
AF:
0.000128
AC:
187
AN:
1455824
Hom.:
0
Cov.:
31
AF XY:
0.000116
AC XY:
84
AN XY:
723986
show subpopulations
African (AFR)
AF:
0.00245
AC:
81
AN:
33078
American (AMR)
AF:
0.00113
AC:
49
AN:
43490
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25922
East Asian (EAS)
AF:
0.0000760
AC:
3
AN:
39480
South Asian (SAS)
AF:
0.0000355
AC:
3
AN:
84476
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53336
Middle Eastern (MID)
AF:
0.000174
AC:
1
AN:
5734
European-Non Finnish (NFE)
AF:
0.0000261
AC:
29
AN:
1110152
Other (OTH)
AF:
0.000349
AC:
21
AN:
60156
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.480
Heterozygous variant carriers
0
8
16
23
31
39
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000902
AC:
137
AN:
151870
Hom.:
0
Cov.:
32
AF XY:
0.000836
AC XY:
62
AN XY:
74180
show subpopulations
African (AFR)
AF:
0.00302
AC:
125
AN:
41418
American (AMR)
AF:
0.000262
AC:
4
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.000387
AC:
2
AN:
5172
South Asian (SAS)
AF:
0.000208
AC:
1
AN:
4800
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10490
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000736
AC:
5
AN:
67962
Other (OTH)
AF:
0.00
AC:
0
AN:
2100
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
7
15
22
30
37
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000715
Hom.:
0
Bravo
AF:
0.000895
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

CHN2-related disorder Benign:1
Jul 26, 2022
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as likely 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
-0.34
CADD
Benign
6.0
DANN
Benign
0.53
PhyloP100
-1.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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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Other links and lift over

dbSNP: rs148176559; hg19: chr7-29546857; COSMIC: COSV108074315; COSMIC: COSV108074315; API