NM_004067.4:c.611A>G

Variant names:

• chr7-29480313-A-G
• rs3750103
• NM_004067.4:c.611A>G

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 19 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	NM_004067.4	MANE Select	c.611A>G	p.His204Arg	missense	Exon 7 of 13	NP_004058.1	P52757-1
	CHN2	NM_001293070.2		c.650A>G	p.His217Arg	missense	Exon 8 of 14	NP_001279999.1	B7Z1V0
	CHN2	NM_001293072.2		c.566A>G	p.His189Arg	missense	Exon 7 of 13	NP_001280001.1	B7Z1W9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	ENST00000222792.11	TSL:1 MANE Select	c.611A>G	p.His204Arg	missense	Exon 7 of 13	ENSP00000222792.7	P52757-1
	CHN2	ENST00000421775.6	TSL:1	c.203A>G	p.His68Arg	missense	Exon 1 of 6	ENSP00000394284.2	P52757-5
	CHN2	ENST00000409041.8	TSL:1	c.203A>G	p.His68Arg	missense	Exon 1 of 5	ENSP00000386849.5	B3VCF5

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

GnomAD2 exomes AF: 0.0884 AC: 22228 AN: 251426 AF XY: 0.0841

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 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

African (AFR) AF: 0.154 AC: 5140 AN: 33476

American (AMR) AF: 0.144 AC: 6420 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2884 AN: 26136

East Asian (EAS) AF: 0.208 AC: 8265 AN: 39700

South Asian (SAS) AF: 0.0759 AC: 6549 AN: 86258

European-Finnish (FIN) AF: 0.0575 AC: 3072 AN: 53418

Middle Eastern (MID) AF: 0.113 AC: 652 AN: 5766

European-Non Finnish (NFE) AF: 0.0471 AC: 52411 AN: 1111958

Other (OTH) AF: 0.0707 AC: 4272 AN: 60396

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

African (AFR) AF: 0.155 AC: 6424 AN: 41498

American (AMR) AF: 0.125 AC: 1912 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 387 AN: 3470

East Asian (EAS) AF: 0.198 AC: 1022 AN: 5172

South Asian (SAS) AF: 0.0770 AC: 370 AN: 4808

European-Finnish (FIN) AF: 0.0624 AC: 662 AN: 10616

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0480 AC: 3267 AN: 68032

Other (OTH) AF: 0.0899 AC: 190 AN: 2114

Alfa AF: 0.0648 Hom.: 1845

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 v4.9

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
Eigen	Benign	-0.19
Eigen_PC	Benign	0.014
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		7.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.18
Sift	Benign	0.20	T
Sift4G	Benign	0.076	T
Polyphen		0.0010	B
Vest4		0.17
MPC		0.38
ClinPred		0.022	T
GERP RS		4.4
PromoterAI		0.0010	Neutral
Varity_R		0.14
gMVP		0.32
Mutation Taster		=90/10	polymorphism (auto)

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

Other links and lift over

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