rs11770859

chr7-29507556-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4	c.1129+191T>G		intron_variant		ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.1129+191T>G		intron_variant		1	NM_004067.4	P1

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

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.379

Alfa AF: 0.351 Hom.: 9682

Bravo AF: 0.420

Asia WGS AF: 0.355 AC: 1235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.017
Dann	Benign	0.54

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: rs11770859; hg19: chr7-29547172; COSMIC: COSV56102424; COSMIC: COSV56102424;