rs3750103

Positions:

• chr7-29480313-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004067.4(CHN2):​c.611A>G​(p.His204Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0644 in 1,614,042 control chromosomes in the GnomAD database, including 4,602 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.094 (857 hom., cov: 32)
  • Exomes 𝑓: 0.061 (3745 hom.)
• Consequence: CHN2 NM_004067.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.98

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00161618).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHN2	NM_004067.4	c.611A>G	p.His204Arg	missense_variant	7/13	ENST00000222792.11	NP_004058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11	c.611A>G	p.His204Arg	missense_variant	7/13	1	NM_004067.4	ENSP00000222792.7

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14269 AN: 152094 Hom.: 854 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.0779

Gnomad FIN AF: 0.0624

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0480

Gnomad OTH AF: 0.0908

GnomAD3 exomes AF: 0.0884 AC: 22228 AN: 251426 Hom.: 1287 AF XY: 0.0841 AC XY: 11434 AN XY: 135896

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.195

Gnomad SAS exome AF: 0.0767

Gnomad FIN exome AF: 0.0601

Gnomad NFE exome AF: 0.0503

Gnomad OTH exome AF: 0.0746

GnomAD4 exome AF: 0.0613 AC: 89665 AN: 1461830 Hom.: 3745 Cov.: 34 AF XY: 0.0616 AC XY: 44781 AN XY: 727218

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.0759

Gnomad4 FIN exome AF: 0.0575

Gnomad4 NFE exome AF: 0.0471

Gnomad4 OTH exome AF: 0.0707

GnomAD4 genome AF: 0.0938 AC: 14281 AN: 152212 Hom.: 857 Cov.: 32 AF XY: 0.0965 AC XY: 7184 AN XY: 74426

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.0770

Gnomad4 FIN AF: 0.0624

Gnomad4 NFE AF: 0.0480

Gnomad4 OTH AF: 0.0899

Alfa AF: 0.0624 Hom.: 843

Bravo AF: 0.102

TwinsUK AF: 0.0448 AC: 166

ALSPAC AF: 0.0516 AC: 199

ESP6500AA AF: 0.146 AC: 642

ESP6500EA AF: 0.0493 AC: 424

ExAC AF: 0.0853 AC: 10355

Asia WGS AF: 0.140 AC: 487 AN: 3478

EpiCase AF: 0.0533

EpiControl AF: 0.0575

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.042	.;T;T;.;.;.;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	0.014
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D;D
MetaRNN	Benign	0.0016	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;N;.;.;.;.;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.81	.;N;.;.;N;N;.;N
REVEL	Benign	0.18
Sift	Benign	0.20	.;T;.;.;D;D;.;D
Sift4G	Benign	0.076	.;T;D;D;D;T;D;D
Polyphen		0.0010, 0.0, 0.019	.;B;.;.;B;.;B;B
Vest4		0.17, 0.12, 0.13, 0.17, 0.21, 0.22, 0.23
MPC		0.38
ClinPred		0.022	T
GERP RS		4.4
Varity_R		0.14
gMVP		0.32

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

Other links and lift over

dbSNP: rs3750103; hg19: chr7-29519929; COSMIC: COSV56093208; COSMIC: COSV56093208;