chr7-29472073-T-C

Position:

• chr7-29472073-T-C

Variant summary

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

The NM_004067.4(CHN2):​c.577-8206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,868 control chromosomes in the GnomAD database, including 16,119 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 0.46 (16119 hom., cov: 31)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHN2	NM_004067.4	c.577-8206T>C		intron_variant		ENST00000222792.11	NP_004058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11	c.577-8206T>C		intron_variant		1	NM_004067.4	ENSP00000222792	P1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69176 AN: 151750 Hom.: 16074 Cov.: 31

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.456 AC: 69280 AN: 151868 Hom.: 16119 Cov.: 31 AF XY: 0.456 AC XY: 33862 AN XY: 74224

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.438

Alfa AF: 0.432 Hom.: 10285

Bravo AF: 0.465

Asia WGS AF: 0.398 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.76
DANN	Benign	0.55

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: rs1362363; hg19: chr7-29511689;