rs1016726

Positions:

• chr7-29316787-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.50-37838G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,044 control chromosomes in the GnomAD database, including 1,329 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 0.12 (1329 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319

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 (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4	c.50-37838G>A		intron_variant		ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.50-37838G>A		intron_variant		1	NM_004067.4	P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18941 AN: 151926 Hom.: 1328 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0817

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0842

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0825

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.125 AC: 18961 AN: 152044 Hom.: 1329 Cov.: 32 AF XY: 0.124 AC XY: 9207 AN XY: 74334

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.0842

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.0826

Gnomad4 FIN AF: 0.0659

Gnomad4 NFE AF: 0.0879

Gnomad4 OTH AF: 0.138

Alfa AF: 0.0984 Hom.: 1676

Bravo AF: 0.136

Asia WGS AF: 0.153 AC: 532 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	4.8
DANN	Benign	0.51

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: rs1016726; hg19: chr7-29356403;