rs1362363

Variant names:

• chr7-29472073-T-C
• rs1362363
• NM_004067.4:c.577-8206T>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.577-8206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,868 control chromosomes in the GnomAD database, including 16,119 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 (16119 hom., cov: 31)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534
• Publications: 6 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]

PRR15-DT (HGNC:55866): (PRR15 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN2	NM_004067.4	c.577-8206T>C		intron_variant	Intron 6 of 12	ENST00000222792.11	NP_004058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11	c.577-8206T>C		intron_variant	Intron 6 of 12	1	NM_004067.4	ENSP00000222792.7

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69176 AN: 151750 Hom.: 16074 Cov.: 31

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.456 AC: 69280 AN: 151868 Hom.: 16119 Cov.: 31 AF XY: 0.456 AC XY: 33862 AN XY: 74224

African (AFR) AF: 0.524 AC: 21707 AN: 41400

American (AMR) AF: 0.494 AC: 7533 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1624 AN: 3470

East Asian (EAS) AF: 0.390 AC: 2015 AN: 5164

South Asian (SAS) AF: 0.391 AC: 1883 AN: 4810

European-Finnish (FIN) AF: 0.408 AC: 4299 AN: 10532

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28608 AN: 67940

Other (OTH) AF: 0.438 AC: 926 AN: 2112

Alfa AF: 0.434 Hom.: 14231

Bravo AF: 0.465

Asia WGS AF: 0.398 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.76
DANN	Benign	0.55
PhyloP100		-0.53
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: rs1362363; hg19: chr7-29511689;