NM_004067.4:c.1129+191T>G

Variant names:

• chr7-29507556-T-G
• rs11770859
• NM_004067.4:c.1129+191T>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.1129+191T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,998 control chromosomes in the GnomAD database, including 13,625 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13625 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 3 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 (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 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.1129+191T>G		intron	N/A	NP_004058.1	P52757-1
	CHN2	NM_001293070.2		c.1168+191T>G		intron	N/A	NP_001279999.1	B7Z1V0
	CHN2	NM_001293072.2		c.1084+191T>G		intron	N/A	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.1129+191T>G		intron	N/A	ENSP00000222792.7	P52757-1
	CHN2	ENST00000421775.6	TSL:1	c.547+191T>G		intron	N/A	ENSP00000394284.2	P52757-5
	CHN2	ENST00000409041.8	TSL:1	c.506-1745T>G		intron	N/A	ENSP00000386849.5	B3VCF5

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62320 AN: 151880 Hom.: 13609 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.378

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.410 AC: 62382 AN: 151998 Hom.: 13625 Cov.: 32 AF XY: 0.410 AC XY: 30460 AN XY: 74292

African (AFR) AF: 0.561 AC: 23250 AN: 41424

American (AMR) AF: 0.419 AC: 6406 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1354 AN: 3472

East Asian (EAS) AF: 0.363 AC: 1873 AN: 5154

South Asian (SAS) AF: 0.307 AC: 1477 AN: 4816

European-Finnish (FIN) AF: 0.371 AC: 3918 AN: 10572

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22706 AN: 67978

Other (OTH) AF: 0.379 AC: 799 AN: 2106

Alfa AF: 0.362 Hom.: 13483

Bravo AF: 0.420

Asia WGS AF: 0.355 AC: 1235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.017
DANN	Benign	0.54
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs11770859; hg19: chr7-29547172; COSMIC: COSV56102424; COSMIC: COSV56102424;