rs1002630

Variant names:

• chr7-29388454-G-A
• rs1002630
• NM_004067.4:c.145-5225G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004067.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	NM_004067.4	MANE Select	c.145-5225G>A		intron	N/A	NP_004058.1	P52757-1
	CHN2	NM_001293070.2		c.184-5225G>A		intron	N/A	NP_001279999.1	B7Z1V0
	CHN2	NM_001293072.2		c.100-5225G>A		intron	N/A	NP_001280001.1	B7Z1W9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	ENST00000222792.11	TSL:1 MANE Select	c.145-5225G>A		intron	N/A	ENSP00000222792.7	P52757-1
	CHN2	ENST00000706161.1		c.223-5225G>A		intron	N/A	ENSP00000516239.1	A0A994J7L4
	CHN2	ENST00000409350.6	TSL:4	c.184-5225G>A		intron	N/A	ENSP00000386968.2	B7Z1V0

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

African (AFR) AF: 0.122 AC: 5030 AN: 41338

American (AMR) AF: 0.115 AC: 1754 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3468

East Asian (EAS) AF: 0.0773 AC: 397 AN: 5136

South Asian (SAS) AF: 0.200 AC: 953 AN: 4756

European-Finnish (FIN) AF: 0.211 AC: 2224 AN: 10524

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12360 AN: 67928

Other (OTH) AF: 0.146 AC: 307 AN: 2096

Alfa AF: 0.176 Hom.: 1183

Bravo AF: 0.145

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.70
DANN	Benign	0.63
PhyloP100		-0.56
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: rs1002630; hg19: chr7-29428070;