rs2269903

chr7-29207793-A-C

Variant summary

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

The NM_004067.4(CHN2):c.49+12803A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 152,256 control chromosomes in the GnomAD database, including 808 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 0.090 (808 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.543

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=-0.78).
• 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/exons	MANE	UniProt
CHN2	NM_004067.4	c.49+12803A>C		intron_variant		ENST00000222792.11
CHN2-AS1	NR_120522.1	n.158+1020T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.49+12803A>C		intron_variant		1	NM_004067.4	P1
CHN2-AS1	ENST00000446246.1	n.158+1020T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13707 AN: 152138 Hom.: 805 Cov.: 32

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.0713

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.0932

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0700

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

GnomAD4 genome AF: 0.0901 AC: 13713 AN: 152256 Hom.: 808 Cov.: 32 AF XY: 0.0896 AC XY: 6667 AN XY: 74448

Gnomad4 AFR AF: 0.0224

Gnomad4 AMR AF: 0.0713

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.0935

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.0745

Alfa AF: 0.115 Hom.: 1433

Bravo AF: 0.0855

Asia WGS AF: 0.142 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	13
Dann	Benign	0.62

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: rs2269903; hg19: chr7-29247409;