rs3793276

Positions:

• chr7-29369980-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.144+1993A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,108 control chromosomes in the GnomAD database, including 4,799 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 0.23 (4799 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHN2	NM_004067.4	c.144+1993A>G		intron_variant		ENST00000222792.11	NP_004058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11	c.144+1993A>G		intron_variant		1	NM_004067.4	ENSP00000222792.7

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35438 AN: 151990 Hom.: 4789 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.233 AC: 35471 AN: 152108 Hom.: 4799 Cov.: 32 AF XY: 0.229 AC XY: 17016 AN XY: 74330

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.264

Alfa AF: 0.288 Hom.: 8701

Bravo AF: 0.230

Asia WGS AF: 0.235 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.59

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: rs3793276; hg19: chr7-29409596;