rs12112301

Variant names:

• chr7-29398493-C-T
• rs12112301
• NM_004067.4:c.290+7C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004067.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	NM_004067.4	MANE Select	c.290+7C>T		splice_region intron	N/A	NP_004058.1
	CHN2	NM_001293070.2		c.329+7C>T		splice_region intron	N/A	NP_001279999.1
	CHN2	NM_001293072.2		c.245+7C>T		splice_region intron	N/A	NP_001280001.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	ENST00000222792.11	TSL:1 MANE Select	c.290+7C>T		splice_region intron	N/A	ENSP00000222792.7
	CHN2	ENST00000706161.1		c.368+7C>T		splice_region intron	N/A	ENSP00000516239.1
	CHN2	ENST00000409350.6	TSL:4	c.329+7C>T		splice_region intron	N/A	ENSP00000386968.2

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

GnomAD2 exomes AF: 0.0968 AC: 24160 AN: 249588 AF XY: 0.0968

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 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

African (AFR) AF: 0.0991 AC: 3235 AN: 32646

American (AMR) AF: 0.112 AC: 4999 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 1419 AN: 25880

East Asian (EAS) AF: 0.153 AC: 6029 AN: 39516

South Asian (SAS) AF: 0.121 AC: 10374 AN: 85468

European-Finnish (FIN) AF: 0.0778 AC: 4030 AN: 51816

Middle Eastern (MID) AF: 0.0980 AC: 555 AN: 5664

European-Non Finnish (NFE) AF: 0.0812 AC: 87274 AN: 1075330

Other (OTH) AF: 0.0874 AC: 5159 AN: 59022

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

African (AFR) AF: 0.0993 AC: 4125 AN: 41522

American (AMR) AF: 0.113 AC: 1726 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3472

East Asian (EAS) AF: 0.174 AC: 902 AN: 5172

South Asian (SAS) AF: 0.123 AC: 593 AN: 4804

European-Finnish (FIN) AF: 0.0734 AC: 778 AN: 10594

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0811 AC: 5518 AN: 68014

Other (OTH) AF: 0.0948 AC: 200 AN: 2110

Alfa AF: 0.0837 Hom.: 2263

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.84
DANN	Benign	0.42
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12112301; hg19: chr7-29438109; COSMIC: COSV56092788; COSMIC: COSV56092788;