rs39118

Positions:

• chr7-29314416-C-A
• chr7-29314416-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004067.4(CHN2):​c.50-40209C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,242 control chromosomes in the GnomAD database, including 61,361 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 0.90 (61361 hom., cov: 32)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4	c.50-40209C>A		intron_variant		ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.50-40209C>A		intron_variant		1	NM_004067.4	P1

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136441 AN: 152124 Hom.: 61307 Cov.: 32

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.789

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.847

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.899

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

GnomAD4 genome AF: 0.897 AC: 136553 AN: 152242 Hom.: 61361 Cov.: 32 AF XY: 0.897 AC XY: 66759 AN XY: 74424

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.915

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.790

Gnomad4 FIN AF: 0.900

Gnomad4 NFE AF: 0.882

Gnomad4 OTH AF: 0.901

Alfa AF: 0.873 Hom.: 22816

Bravo AF: 0.904

Asia WGS AF: 0.903 AC: 3140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.010
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs39118; hg19: chr7-29354032;