rs17157658

Variant names:

• chr7-29234638-G-C
• rs17157658
• NM_004067.4:c.49+39648G>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.49+39648G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 152,228 control chromosomes in the GnomAD database, including 463 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 0.052 (463 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19
• Publications: 2 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=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	NM_004067.4	MANE Select	c.49+39648G>C		intron	N/A	NP_004058.1
	CHN2	NM_001293070.2		c.49+39648G>C		intron	N/A	NP_001279999.1
	CHN2	NM_001293072.2		c.4+36655G>C		intron	N/A	NP_001280001.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	ENST00000222792.11	TSL:1 MANE Select	c.49+39648G>C		intron	N/A	ENSP00000222792.7
	CHN2	ENST00000706161.1		c.49+39648G>C		intron	N/A	ENSP00000516239.1
	CHN2	ENST00000409350.6	TSL:4	c.49+39648G>C		intron	N/A	ENSP00000386968.2

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7902 AN: 152110 Hom.: 459 Cov.: 32

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.0976

Gnomad FIN AF: 0.0722

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0370

Gnomad OTH AF: 0.0608

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

GnomAD4 genome AF: 0.0519 AC: 7907 AN: 152228 Hom.: 463 Cov.: 32 AF XY: 0.0573 AC XY: 4261 AN XY: 74424

African (AFR) AF: 0.0110 AC: 458 AN: 41544

American (AMR) AF: 0.127 AC: 1938 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0651 AC: 226 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1386 AN: 5162

South Asian (SAS) AF: 0.0968 AC: 467 AN: 4822

European-Finnish (FIN) AF: 0.0722 AC: 765 AN: 10594

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0370 AC: 2518 AN: 68030

Other (OTH) AF: 0.0602 AC: 127 AN: 2110

Alfa AF: 0.0432 Hom.: 30

Bravo AF: 0.0553

Asia WGS AF: 0.162 AC: 564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.82
PhyloP100		3.2
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: rs17157658; hg19: chr7-29274254;