7-29499961-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_004067.4(CHN2):c.834C>T(p.Asp278=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000743 in 1,610,582 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00087 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (3 hom.)
• Consequence: CHN2 NM_004067.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.259

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 7-29499961-C-T is Benign according to our data. Variant chr7-29499961-C-T is described in ClinVar as [Benign]. Clinvar id is 3033891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.259 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHN2	NM_004067.4	c.834C>T	p.Asp278=	synonymous_variant	9/13	ENST00000222792.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHN2	ENST00000222792.11	c.834C>T	p.Asp278=	synonymous_variant	9/13	1	NM_004067.4	P1

Frequencies

GnomAD3 genomes AF: 0.000869 AC: 132 AN: 151908 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000629

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00122 AC: 304 AN: 249328 Hom.: 0 AF XY: 0.00105 AC XY: 141 AN XY: 134780

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00204

Gnomad ASJ exome AF: 0.0108

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000432

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000804

Gnomad OTH exome AF: 0.00362

GnomAD4 exome AF: 0.000729 AC: 1063 AN: 1458556 Hom.: 3 Cov.: 30 AF XY: 0.000730 AC XY: 530 AN XY: 725552

Gnomad4 AFR exome AF: 0.000300

Gnomad4 AMR exome AF: 0.00227

Gnomad4 ASJ exome AF: 0.0112

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000572

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000410

Gnomad4 OTH exome AF: 0.00181

GnomAD4 genome AF: 0.000875 AC: 133 AN: 152026 Hom.: 1 Cov.: 32 AF XY: 0.000794 AC XY: 59 AN XY: 74300

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.00210

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000629

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000736

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00144 Hom.: 1

Bravo AF: 0.00125

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000984

EpiControl AF: 0.000712

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CHN2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	10
Dann	Benign	0.57

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: rs145906178; hg19: chr7-29539577;