chr7-29512640-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004067.4(CHN2):​c.1312C>T​(p.Pro438Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,614,034 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.013 ( 57 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 38 hom. )

Consequence

CHN2
NM_004067.4 missense

Scores

3
15

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.667
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)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004365593).
BP6
Variant 7-29512640-C-T is Benign according to our data. Variant chr7-29512640-C-T is described in ClinVar as [Benign]. Clinvar id is 776213.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2032/152248) while in subpopulation AFR AF= 0.0463 (1922/41532). AF 95% confidence interval is 0.0446. There are 57 homozygotes in gnomad4. There are 973 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHN2NM_004067.4 linkc.1312C>T p.Pro438Ser missense_variant Exon 13 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.1312C>T p.Pro438Ser missense_variant Exon 13 of 13 1 NM_004067.4 ENSP00000222792.7 P52757-1

Frequencies

GnomAD3 genomes
AF:
0.0133
AC:
2025
AN:
152132
Hom.:
57
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0462
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00465
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.0134
GnomAD3 exomes
AF:
0.00375
AC:
942
AN:
251260
Hom.:
26
AF XY:
0.00281
AC XY:
382
AN XY:
135796
show subpopulations
Gnomad AFR exome
AF:
0.0497
Gnomad AMR exome
AF:
0.00310
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00140
AC:
2051
AN:
1461786
Hom.:
38
Cov.:
31
AF XY:
0.00118
AC XY:
859
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.0494
Gnomad4 AMR exome
AF:
0.00327
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000639
Gnomad4 OTH exome
AF:
0.00273
GnomAD4 genome
AF:
0.0133
AC:
2032
AN:
152248
Hom.:
57
Cov.:
32
AF XY:
0.0131
AC XY:
973
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0463
Gnomad4 AMR
AF:
0.00464
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.0133
Alfa
AF:
0.00232
Hom.:
18
Bravo
AF:
0.0158
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.0529
AC:
233
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.00438
AC:
532
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
May 25, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

CHN2-related disorder Benign:1
Mar 26, 2019
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as 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
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
15
DANN
Benign
0.82
DEOGEN2
Benign
0.083
.;T;.;.;.;.
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.13
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.87
D;D;D;D;D;D
MetaRNN
Benign
0.0044
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.69
.;N;.;.;.;.
PrimateAI
Uncertain
0.48
T
PROVEAN
Benign
-1.2
.;N;.;N;.;.
REVEL
Benign
0.062
Sift
Benign
1.0
.;T;.;T;.;.
Sift4G
Benign
0.48
.;T;T;T;T;T
Polyphen
0.0010, 0.017, 0.77
.;B;.;.;B;P
Vest4
0.11, 0.13, 0.21, 0.098, 0.10
MVP
0.48
MPC
0.32
ClinPred
0.0036
T
GERP RS
4.5
Varity_R
0.31
gMVP
0.56

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

LitVar

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

Other links and lift over

dbSNP: rs34971642; hg19: chr7-29552256; COSMIC: COSV56095812; COSMIC: COSV56095812; API