NM_004067.4:c.49+14592G>C

Variant names:

• chr7-29209582-G-C
• rs3812388
• NM_004067.4:c.49+14592G>C

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+14592G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,162 control chromosomes in the GnomAD database, including 1,034 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 (1034 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 2 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN2	NM_004067.4	c.49+14592G>C		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+14592G>C		intron_variant	Intron 1 of 12	1	NM_004067.4	ENSP00000222792.7

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17388 AN: 152044 Hom.: 1033 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0920

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

GnomAD4 genome AF: 0.114 AC: 17399 AN: 152162 Hom.: 1034 Cov.: 32 AF XY: 0.112 AC XY: 8345 AN XY: 74378

African (AFR) AF: 0.109 AC: 4543 AN: 41518

American (AMR) AF: 0.0789 AC: 1206 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1042 AN: 5172

South Asian (SAS) AF: 0.0827 AC: 398 AN: 4810

European-Finnish (FIN) AF: 0.107 AC: 1133 AN: 10592

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8490 AN: 68000

Other (OTH) AF: 0.0957 AC: 202 AN: 2110

Alfa AF: 0.0686 Hom.: 86

Bravo AF: 0.114

Asia WGS AF: 0.140 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.74
PhyloP100		0.29
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: rs3812388; hg19: chr7-29249198;