7-29254846-A-G

Variant names:

• chr7-29254846-A-G
• rs39101
• NM_004067.4:c.49+59856A>G

Variant summary

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

The NM_004067.4(CHN2):​c.49+59856A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,940 control chromosomes in the GnomAD database, including 35,129 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 0.66 (35129 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 6 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN2	NM_004067.4	c.49+59856A>G		intron_variant	Intron 1 of 12	ENST00000222792.11	NP_004058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11	c.49+59856A>G		intron_variant	Intron 1 of 12	1	NM_004067.4	ENSP00000222792.7

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100482 AN: 151822 Hom.: 35118 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.662 AC: 100525 AN: 151940 Hom.: 35129 Cov.: 32 AF XY: 0.661 AC XY: 49056 AN XY: 74236

African (AFR) AF: 0.428 AC: 17707 AN: 41414

American (AMR) AF: 0.783 AC: 11965 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2492 AN: 3472

East Asian (EAS) AF: 0.848 AC: 4356 AN: 5134

South Asian (SAS) AF: 0.597 AC: 2874 AN: 4812

European-Finnish (FIN) AF: 0.727 AC: 7663 AN: 10546

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.751 AC: 51073 AN: 67968

Other (OTH) AF: 0.676 AC: 1427 AN: 2112

Alfa AF: 0.731 Hom.: 72127

Bravo AF: 0.659

Asia WGS AF: 0.696 AC: 2420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.3
DANN	Benign	0.79
PhyloP100		0.019
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: rs39101; hg19: chr7-29294462;