chr7-29508708-T-C

Variant names:

• chr7-29508708-T-C
• rs1420143
• NM_004067.4:c.1130-593T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000222792.11(CHN2):​c.1130-593T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,740 control chromosomes in the GnomAD database, including 16,966 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 0.47 (16966 hom., cov: 31)
• Consequence: CHN2 ENST00000222792.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• 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]

PRR15-DT (HGNC:55866): (PRR15 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000222792.11. 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.1130-593T>C		intron	N/A	NP_004058.1
	CHN2	NM_001293070.2		c.1169-593T>C		intron	N/A	NP_001279999.1
	CHN2	NM_001293072.2		c.1085-593T>C		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.1130-593T>C		intron	N/A	ENSP00000222792.7
	CHN2	ENST00000421775.6	TSL:1	c.548-593T>C		intron	N/A	ENSP00000394284.2
	CHN2	ENST00000409041.8	TSL:1	c.506-593T>C		intron	N/A	ENSP00000386849.5

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70512 AN: 151622 Hom.: 16946 Cov.: 31

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.465 AC: 70575 AN: 151740 Hom.: 16966 Cov.: 31 AF XY: 0.461 AC XY: 34207 AN XY: 74178

African (AFR) AF: 0.583 AC: 24035 AN: 41216

American (AMR) AF: 0.492 AC: 7519 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3466

East Asian (EAS) AF: 0.198 AC: 1017 AN: 5144

South Asian (SAS) AF: 0.351 AC: 1686 AN: 4810

European-Finnish (FIN) AF: 0.389 AC: 4112 AN: 10578

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.432 AC: 29362 AN: 67950

Other (OTH) AF: 0.466 AC: 982 AN: 2108

Alfa AF: 0.443 Hom.: 28325

Bravo AF: 0.479

Asia WGS AF: 0.318 AC: 1106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.079
DANN	Benign	0.63
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1420143; hg19: chr7-29548324;