rs39099

Variant names:

• chr7-29253479-G-A
• rs39099
• NM_004067.4:c.49+58489G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004067.4(CHN2):​c.49+58489G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,106 control chromosomes in the GnomAD database, including 6,287 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 0.27 (6287 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN2	NM_004067.4	c.49+58489G>A		intron_variant	Intron 1 of 12	ENST00000222792.11	NP_004058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11	c.49+58489G>A		intron_variant	Intron 1 of 12	1	NM_004067.4	ENSP00000222792.7

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40416 AN: 151988 Hom.: 6283 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.266 AC: 40417 AN: 152106 Hom.: 6287 Cov.: 32 AF XY: 0.267 AC XY: 19878 AN XY: 74338

African (AFR) AF: 0.0997 AC: 4139 AN: 41522

American (AMR) AF: 0.336 AC: 5134 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1168 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1389 AN: 5158

South Asian (SAS) AF: 0.273 AC: 1316 AN: 4820

European-Finnish (FIN) AF: 0.365 AC: 3849 AN: 10548

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22423 AN: 67982

Other (OTH) AF: 0.282 AC: 596 AN: 2114

Alfa AF: 0.314 Hom.: 13243

Bravo AF: 0.256

Asia WGS AF: 0.244 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.3
DANN	Benign	0.81
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs39099; hg19: chr7-29293095;