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7-29507241-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_004067.4(CHN2):c.1005C>T(p.Ala335=) 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 (★).

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 criteria provided, single submitter 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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.59 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHN2NM_004067.4 linkuse as main transcriptc.1005C>T p.Ala335= synonymous_variant 11/13 ENST00000222792.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHN2ENST00000222792.11 linkuse as main transcriptc.1005C>T p.Ala335= synonymous_variant 11/131 NM_004067.4 P1P52757-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 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
GnomAD3 exomes
AF:
0.000368
AC:
90
AN:
244376
Hom.:
0
AF XY:
0.000280
AC XY:
37
AN XY:
131950
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 SAS exome
AF:
0.0000699
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
Gnomad4 AFR exome
AF:
0.00245
Gnomad4 AMR exome
AF:
0.00113
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000760
Gnomad4 SAS exome
AF:
0.0000355
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.000349
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000902
AC:
137
AN:
151870
Hom.:
0
Cov.:
32
AF XY:
0.000836
AC XY:
62
AN XY:
74180
show subpopulations
Gnomad4 AFR
AF:
0.00302
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000736
Gnomad4 OTH
AF:
0.00
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

CHN2-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 26, 2022This 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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148176559; hg19: chr7-29546857; API