NM_004067.4:c.49+3388A>G

Variant names:

• chr7-29198378-A-G
• rs3812398
• NM_004067.4:c.49+3388A>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+3388A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,270 control chromosomes in the GnomAD database, including 1,180 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 0.11 (1180 hom., cov: 33)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN2	NM_004067.4	c.49+3388A>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+3388A>G		intron_variant	Intron 1 of 12	1	NM_004067.4	ENSP00000222792.7

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16450 AN: 152154 Hom.: 1175 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0828

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0662

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.108 AC: 16473 AN: 152270 Hom.: 1180 Cov.: 33 AF XY: 0.111 AC XY: 8250 AN XY: 74448

African (AFR) AF: 0.145 AC: 6041 AN: 41556

American (AMR) AF: 0.168 AC: 2569 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0828 AC: 287 AN: 3466

East Asian (EAS) AF: 0.290 AC: 1504 AN: 5180

South Asian (SAS) AF: 0.161 AC: 776 AN: 4828

European-Finnish (FIN) AF: 0.0406 AC: 431 AN: 10610

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0662 AC: 4501 AN: 68016

Other (OTH) AF: 0.121 AC: 256 AN: 2110

Alfa AF: 0.0835 Hom.: 2729

Bravo AF: 0.121

Asia WGS AF: 0.211 AC: 732 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	0.0050
DANN	Benign	0.39
PhyloP100		-1.1
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: rs3812398; hg19: chr7-29237994;