rs245962

Variant names:

• chr7-29250537-A-G
• rs245962
• NM_004067.4:c.49+55547A>G

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+55547A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,004 control chromosomes in the GnomAD database, including 18,314 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 0.46 (18314 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN2	NM_004067.4	c.49+55547A>G		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+55547A>G		intron_variant	Intron 1 of 12	1	NM_004067.4	ENSP00000222792.7

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69536 AN: 151884 Hom.: 18275 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.458 AC: 69630 AN: 152004 Hom.: 18314 Cov.: 32 AF XY: 0.453 AC XY: 33688 AN XY: 74312

African (AFR) AF: 0.724 AC: 30038 AN: 41472

American (AMR) AF: 0.433 AC: 6618 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3468

East Asian (EAS) AF: 0.538 AC: 2774 AN: 5154

South Asian (SAS) AF: 0.254 AC: 1221 AN: 4816

European-Finnish (FIN) AF: 0.313 AC: 3304 AN: 10558

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23436 AN: 67942

Other (OTH) AF: 0.447 AC: 946 AN: 2114

Alfa AF: 0.376 Hom.: 19863

Bravo AF: 0.485

Asia WGS AF: 0.438 AC: 1522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.62
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs245962; hg19: chr7-29290153;