rs245955

Variant names:

• chr7-29236691-C-T
• rs245955
• NM_004067.4:c.49+41701C>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+41701C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,154 control chromosomes in the GnomAD database, including 4,723 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 0.24 (4723 hom., cov: 33)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN2	NM_004067.4	c.49+41701C>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+41701C>T		intron_variant	Intron 1 of 12	1	NM_004067.4	ENSP00000222792.7

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35828 AN: 152036 Hom.: 4712 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.236 AC: 35858 AN: 152154 Hom.: 4723 Cov.: 33 AF XY: 0.237 AC XY: 17629 AN XY: 74376

African (AFR) AF: 0.286 AC: 11872 AN: 41494

American (AMR) AF: 0.284 AC: 4337 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3464

East Asian (EAS) AF: 0.528 AC: 2737 AN: 5180

South Asian (SAS) AF: 0.215 AC: 1032 AN: 4808

European-Finnish (FIN) AF: 0.144 AC: 1525 AN: 10602

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12947 AN: 68002

Other (OTH) AF: 0.247 AC: 522 AN: 2112

Alfa AF: 0.209 Hom.: 722

Bravo AF: 0.251

Asia WGS AF: 0.374 AC: 1302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.25
PhyloP100		-0.61
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: rs245955; hg19: chr7-29276307;