rs1016726

Variant names:

• chr7-29316787-G-A
• rs1016726
• NM_004067.4:c.50-37838G>A

Variant summary

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

The NM_004067.4(CHN2):​c.50-37838G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,044 control chromosomes in the GnomAD database, including 1,329 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 0.12 (1329 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.319
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 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.50-37838G>A		intron	N/A	NP_004058.1
	CHN2	NM_001293070.2		c.88+23824G>A		intron	N/A	NP_001279999.1
	CHN2	NM_001293072.2		c.5-37838G>A		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.50-37838G>A		intron	N/A	ENSP00000222792.7
	CHN2	ENST00000706161.1		c.127+23179G>A		intron	N/A	ENSP00000516239.1
	CHN2	ENST00000409350.6	TSL:4	c.88+23824G>A		intron	N/A	ENSP00000386968.2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18941 AN: 151926 Hom.: 1328 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0817

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0842

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0825

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.125 AC: 18961 AN: 152044 Hom.: 1329 Cov.: 32 AF XY: 0.124 AC XY: 9207 AN XY: 74334

African (AFR) AF: 0.187 AC: 7737 AN: 41430

American (AMR) AF: 0.157 AC: 2393 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0842 AC: 292 AN: 3468

East Asian (EAS) AF: 0.203 AC: 1050 AN: 5182

South Asian (SAS) AF: 0.0826 AC: 398 AN: 4820

European-Finnish (FIN) AF: 0.0659 AC: 697 AN: 10572

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0879 AC: 5976 AN: 67986

Other (OTH) AF: 0.138 AC: 291 AN: 2114

Alfa AF: 0.103 Hom.: 2951

Bravo AF: 0.136

Asia WGS AF: 0.153 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.51
PhyloP100		0.32
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: rs1016726; hg19: chr7-29356403;