rs12112301

chr7-29398493-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.290+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 1,572,172 control chromosomes in the GnomAD database, including 6,458 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.093 (730 hom., cov: 32)
  • Exomes 𝑓: 0.087 (5728 hom.)
• Consequence: CHN2 NM_004067.4 splice_region, intron
• Scores: Splicing: ADA: 0.0002304
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.997

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4	c.290+7C>T		splice_region_variant, intron_variant		ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.290+7C>T		splice_region_variant, intron_variant		1	NM_004067.4	P1

Frequencies

GnomAD3 genomes AF: 0.0926 AC: 14088 AN: 152072 Hom.: 727 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0953

GnomAD3 exomes AF: 0.0968 AC: 24160 AN: 249588 Hom.: 1368 AF XY: 0.0968 AC XY: 13067 AN XY: 134956

Gnomad AFR exome AF: 0.0953

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.0549

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.118

Gnomad FIN exome AF: 0.0762

Gnomad NFE exome AF: 0.0822

Gnomad OTH exome AF: 0.0915

GnomAD4 exome AF: 0.0867 AC: 123074 AN: 1419982 Hom.: 5728 Cov.: 25 AF XY: 0.0878 AC XY: 62264 AN XY: 709258

Gnomad4 AFR exome AF: 0.0991

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.0548

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.0778

Gnomad4 NFE exome AF: 0.0812

Gnomad4 OTH exome AF: 0.0874

GnomAD4 genome AF: 0.0927 AC: 14106 AN: 152190 Hom.: 730 Cov.: 32 AF XY: 0.0940 AC XY: 6992 AN XY: 74390

Gnomad4 AFR AF: 0.0993

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0734

Gnomad4 NFE AF: 0.0811

Gnomad4 OTH AF: 0.0948

Alfa AF: 0.0818 Hom.: 1026

Bravo AF: 0.0947

Asia WGS AF: 0.147 AC: 509 AN: 3478

EpiCase AF: 0.0772

EpiControl AF: 0.0784

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.84
Dann	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00023
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.040		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: rs12112301; hg19: chr7-29438109; COSMIC: COSV56092788; COSMIC: COSV56092788;