rs17756941

chr7-29210391-A-G

Variant summary

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

The NM_004067.4(CHN2):c.49+15401A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 151,842 control chromosomes in the GnomAD database, including 4,386 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 0.24 (4386 hom., cov: 31)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.773

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4	c.49+15401A>G		intron_variant		ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.49+15401A>G		intron_variant		1	NM_004067.4	P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35675 AN: 151726 Hom.: 4378 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.235 AC: 35686 AN: 151842 Hom.: 4386 Cov.: 31 AF XY: 0.229 AC XY: 16986 AN XY: 74212

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.241

Alfa AF: 0.259 Hom.: 5123

Bravo AF: 0.234

Asia WGS AF: 0.163 AC: 567 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.4
Dann	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs17756941; hg19: chr7-29250007;