rs39075

Positions:

• chr7-29237076-G-A
• chr7-29237076-G-C
• chr7-29237076-G-T

Variant summary

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

The NM_004067.4(CHN2):​c.49+42086G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,026 control chromosomes in the GnomAD database, including 13,075 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 (13075 hom., cov: 33)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4	c.49+42086G>A		intron_variant		ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.49+42086G>A		intron_variant		1	NM_004067.4	P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62666 AN: 151908 Hom.: 13059 Cov.: 33

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.413 AC: 62725 AN: 152026 Hom.: 13075 Cov.: 33 AF XY: 0.410 AC XY: 30492 AN XY: 74296

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.404

Alfa AF: 0.404 Hom.: 6444

Bravo AF: 0.416

Asia WGS AF: 0.382 AC: 1331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.8
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: rs39075; hg19: chr7-29276692;