rs2023908

chr7-29287910-C-Achr7-29287910-C-T

Variant summary

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

The NM_004067.4(CHN2):c.50-66715C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,022 control chromosomes in the GnomAD database, including 42,337 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 0.74 (42337 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.757

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4	c.50-66715C>A		intron_variant		ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.50-66715C>A		intron_variant		1	NM_004067.4	P1

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112972 AN: 151904 Hom.: 42316 Cov.: 32

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.744 AC: 113044 AN: 152022 Hom.: 42337 Cov.: 32 AF XY: 0.744 AC XY: 55269 AN XY: 74290

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.838

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.681

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.748

Alfa AF: 0.775 Hom.: 61864

Bravo AF: 0.738

Asia WGS AF: 0.729 AC: 2533 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.8
Dann	Benign	0.60

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: rs2023908; hg19: chr7-29327526;