rs3812389

Positions:

• chr7-29205143-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004067.4(CHN2):​c.49+10153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,212 control chromosomes in the GnomAD database, including 2,693 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 0.18 (2693 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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]

CHN2-AS1 (HGNC:40149): (CHN2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHN2	NM_004067.4	c.49+10153C>T		intron_variant		ENST00000222792.11	NP_004058.1
CHN2-AS1	NR_120522.1	n.158+3670G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11	c.49+10153C>T		intron_variant		1	NM_004067.4	ENSP00000222792	P1
CHN2-AS1	ENST00000446246.1	n.158+3670G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27109 AN: 152094 Hom.: 2689 Cov.: 32

Gnomad AFR AF: 0.0872

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.178 AC: 27115 AN: 152212 Hom.: 2693 Cov.: 32 AF XY: 0.175 AC XY: 13001 AN XY: 74426

Gnomad4 AFR AF: 0.0872

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.203

Alfa AF: 0.216 Hom.: 7628

Bravo AF: 0.180

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.0
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs3812389; hg19: chr7-29244759;