chr7-29512875-G-A

Variant names:

• chr7-29512875-G-A
• rs73084484
• NM_004067.4:c.*140G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004067.4(CHN2):​c.*140G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 899,440 control chromosomes in the GnomAD database, including 111 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 0.011 (19 hom., cov: 32)
  • Exomes 𝑓: 0.014 (92 hom.)
• Consequence: CHN2 NM_004067.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477

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]

PRR15-DT (HGNC:55866): (PRR15 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0109 (1655/152280) while in subpopulation NFE AF= 0.0165 (1125/68036). AF 95% confidence interval is 0.0157. There are 19 homozygotes in gnomad4. There are 783 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHN2	NM_004067.4	c.*140G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000222792.11	NP_004058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHN2	ENST00000222792.11	c.*140G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_004067.4	ENSP00000222792.7

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1656 AN: 152162 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00266

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.0138 AC: 10345 AN: 747160 Hom.: 92 Cov.: 10 AF XY: 0.0136 AC XY: 5138 AN XY: 379046

Gnomad4 AFR exome AF: 0.00221

Gnomad4 AMR exome AF: 0.00721

Gnomad4 ASJ exome AF: 0.000705

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00231

Gnomad4 FIN exome AF: 0.0256

Gnomad4 NFE exome AF: 0.0162

Gnomad4 OTH exome AF: 0.0104

GnomAD4 genome AF: 0.0109 AC: 1655 AN: 152280 Hom.: 19 Cov.: 32 AF XY: 0.0105 AC XY: 783 AN XY: 74438

Gnomad4 AFR AF: 0.00265

Gnomad4 AMR AF: 0.00804

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.0133 Hom.: 6

Bravo AF: 0.00940

Asia WGS AF: 0.00260 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.66

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: rs73084484; hg19: chr7-29552491;