rs3793275

Variant names:

• chr7-29387134-A-T
• rs3793275
• NM_004067.4:c.145-6545A>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.145-6545A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 152,220 control chromosomes in the GnomAD database, including 381 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 0.069 (381 hom., cov: 33)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN2	NM_004067.4	c.145-6545A>T		intron_variant	Intron 3 of 12	ENST00000222792.11	NP_004058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11	c.145-6545A>T		intron_variant	Intron 3 of 12	1	NM_004067.4	ENSP00000222792.7

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10443 AN: 152102 Hom.: 381 Cov.: 33

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.0429

Gnomad FIN AF: 0.0869

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0597

Gnomad OTH AF: 0.0635

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

GnomAD4 genome AF: 0.0686 AC: 10443 AN: 152220 Hom.: 381 Cov.: 33 AF XY: 0.0694 AC XY: 5164 AN XY: 74432

African (AFR) AF: 0.0929 AC: 3859 AN: 41530

American (AMR) AF: 0.0529 AC: 808 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3470

East Asian (EAS) AF: 0.0164 AC: 85 AN: 5178

South Asian (SAS) AF: 0.0422 AC: 203 AN: 4816

European-Finnish (FIN) AF: 0.0869 AC: 922 AN: 10604

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0597 AC: 4058 AN: 68012

Other (OTH) AF: 0.0633 AC: 134 AN: 2116

Alfa AF: 0.0635 Hom.: 35

Bravo AF: 0.0664

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.56
PhyloP100		0.22
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: rs3793275; hg19: chr7-29426750;