rs39068

Positions:

• chr7-29227971-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.49+32981A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 151,920 control chromosomes in the GnomAD database, including 39,804 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 0.72 (39804 hom., cov: 30)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4	c.49+32981A>G		intron_variant		ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.49+32981A>G		intron_variant		1	NM_004067.4	P1

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109058 AN: 151802 Hom.: 39744 Cov.: 30

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.719 AC: 109183 AN: 151920 Hom.: 39804 Cov.: 30 AF XY: 0.717 AC XY: 53234 AN XY: 74262

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.781

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.724

Alfa AF: 0.687 Hom.: 5595

Bravo AF: 0.740

Asia WGS AF: 0.689 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.062
DANN	Benign	0.73

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: rs39068; hg19: chr7-29267587;