rs1002630

Positions:

• chr7-29388454-G-A

Variant summary

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

The NM_004067.4(CHN2):​c.145-5225G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 151,638 control chromosomes in the GnomAD database, including 2,028 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 0.16 (2028 hom., cov: 33)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHN2	NM_004067.4	c.145-5225G>A		intron_variant		ENST00000222792.11	NP_004058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11	c.145-5225G>A		intron_variant		1	NM_004067.4	ENSP00000222792	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23825 AN: 151520 Hom.: 2027 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.0771

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.157 AC: 23840 AN: 151638 Hom.: 2028 Cov.: 33 AF XY: 0.158 AC XY: 11736 AN XY: 74060

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.0773

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.146

Alfa AF: 0.179 Hom.: 1073

Bravo AF: 0.145

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.70
DANN	Benign	0.63

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: rs1002630; hg19: chr7-29428070;