rs39059

Positions:

• chr7-29215854-A-G

Variant summary

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

The ENST00000222792.11(CHN2):​c.49+20864A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,910 control chromosomes in the GnomAD database, including 8,624 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 0.33 (8624 hom., cov: 31)
• Consequence: CHN2 ENST00000222792.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHN2	NM_004067.4	c.49+20864A>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.49+20864A>G		intron_variant		1	NM_004067.4	ENSP00000222792	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49398 AN: 151792 Hom.: 8623 Cov.: 31

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.325 AC: 49416 AN: 151910 Hom.: 8624 Cov.: 31 AF XY: 0.327 AC XY: 24254 AN XY: 74240

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.462

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.343

Alfa AF: 0.346 Hom.: 2318

Bravo AF: 0.321

Asia WGS AF: 0.358 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.44

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: rs39059; hg19: chr7-29255470;