rs11981737

chr7-29210719-G-Achr7-29210719-G-T

Variant summary

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

The NM_004067.4(CHN2):c.49+15729G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,924 control chromosomes in the GnomAD database, including 4,852 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 0.25 (4852 hom., cov: 31)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

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 (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4	c.49+15729G>A		intron_variant		ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.49+15729G>A		intron_variant		1	NM_004067.4	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37843 AN: 151810 Hom.: 4847 Cov.: 31

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.249 AC: 37869 AN: 151924 Hom.: 4852 Cov.: 31 AF XY: 0.252 AC XY: 18704 AN XY: 74290

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.272

Alfa AF: 0.228 Hom.: 3684

Bravo AF: 0.259

Asia WGS AF: 0.331 AC: 1148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.2
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: rs11981737; hg19: chr7-29250335;