NM_004067.4:c.49+43317C>T

Variant names:

• chr7-29238307-C-T
• rs39076
• NM_004067.4:c.49+43317C>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+43317C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,912 control chromosomes in the GnomAD database, including 10,045 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 0.35 (10045 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 3 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN2	NM_004067.4	c.49+43317C>T		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+43317C>T		intron_variant	Intron 1 of 12	1	NM_004067.4	ENSP00000222792.7

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53419 AN: 151796 Hom.: 10041 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.352 AC: 53447 AN: 151912 Hom.: 10045 Cov.: 32 AF XY: 0.351 AC XY: 26079 AN XY: 74250

African (AFR) AF: 0.217 AC: 8995 AN: 41446

American (AMR) AF: 0.425 AC: 6486 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1671 AN: 3472

East Asian (EAS) AF: 0.384 AC: 1979 AN: 5148

South Asian (SAS) AF: 0.388 AC: 1863 AN: 4804

European-Finnish (FIN) AF: 0.392 AC: 4122 AN: 10516

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.398 AC: 27034 AN: 67964

Other (OTH) AF: 0.359 AC: 753 AN: 2100

Alfa AF: 0.358 Hom.: 1342

Bravo AF: 0.346

Asia WGS AF: 0.363 AC: 1265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.62
DANN	Benign	0.75
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: rs39076; hg19: chr7-29277923;