7-29201829-G-T

Variant names:

• chr7-29201829-G-T
• rs121724
• NM_004067.4:c.49+6839G>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.49+6839G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,076 control chromosomes in the GnomAD database, including 32,814 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 0.64 (32814 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• 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]

CHN2-AS1 (HGNC:40149): (CHN2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 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.49+6839G>T		intron	N/A	NP_004058.1
	CHN2	NM_001293070.2		c.49+6839G>T		intron	N/A	NP_001279999.1
	CHN2	NM_001293072.2		c.4+3846G>T		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.49+6839G>T		intron	N/A	ENSP00000222792.7
	CHN2	ENST00000706161.1		c.49+6839G>T		intron	N/A	ENSP00000516239.1
	CHN2	ENST00000409350.6	TSL:4	c.49+6839G>T		intron	N/A	ENSP00000386968.2

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96848 AN: 151958 Hom.: 32754 Cov.: 32

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.638 AC: 96969 AN: 152076 Hom.: 32814 Cov.: 32 AF XY: 0.636 AC XY: 47237 AN XY: 74318

African (AFR) AF: 0.828 AC: 34367 AN: 41512

American (AMR) AF: 0.712 AC: 10891 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1891 AN: 3468

East Asian (EAS) AF: 0.964 AC: 4976 AN: 5164

South Asian (SAS) AF: 0.585 AC: 2816 AN: 4816

European-Finnish (FIN) AF: 0.442 AC: 4662 AN: 10538

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.520 AC: 35341 AN: 67976

Other (OTH) AF: 0.642 AC: 1355 AN: 2110

Alfa AF: 0.570 Hom.: 76136

Bravo AF: 0.672

Asia WGS AF: 0.783 AC: 2725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.47
PhyloP100		-1.1
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: rs121724; hg19: chr7-29241445;