rs39065

Positions:

• chr7-29222985-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+27995A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,094 control chromosomes in the GnomAD database, including 47,538 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 0.79 (47538 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4	c.49+27995A>G		intron_variant		ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.49+27995A>G		intron_variant		1	NM_004067.4	P1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119639 AN: 151976 Hom.: 47480 Cov.: 32

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.745

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.787 AC: 119758 AN: 152094 Hom.: 47538 Cov.: 32 AF XY: 0.785 AC XY: 58342 AN XY: 74332

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.859

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.799

Alfa AF: 0.756 Hom.: 8855

Bravo AF: 0.807

Asia WGS AF: 0.802 AC: 2792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.63

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: rs39065; hg19: chr7-29262601;