chr7-29371251-G-A

Position:

• chr7-29371251-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.144+3264G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,010 control chromosomes in the GnomAD database, including 5,082 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 (5082 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663

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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHN2	NM_004067.4	c.144+3264G>A		intron_variant		ENST00000222792.11	NP_004058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11	c.144+3264G>A		intron_variant		1	NM_004067.4	ENSP00000222792	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36871 AN: 151892 Hom.: 5078 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.243 AC: 36871 AN: 152010 Hom.: 5082 Cov.: 32 AF XY: 0.241 AC XY: 17865 AN XY: 74270

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.262

Alfa AF: 0.246 Hom.: 697

Bravo AF: 0.235

Asia WGS AF: 0.183 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	16
DANN	Benign	0.80

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: rs7796525; hg19: chr7-29410867;