rs145906178

Variant names:

• chr7-29499961-C-T
• rs145906178
• NM_004067.4:c.834C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-29499961-C-T
• chr7-29499961-C-A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_004067.4(CHN2):​c.834C>T​(p.Asp278Asp) 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.00087 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (3 hom.)
• Consequence: CHN2 NM_004067.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.259
• 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]

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

ACMG classification

Our verdict: Benign. The variant received -8 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 VariationId is 3033891.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.259 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004067.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	NM_004067.4	MANE Select	c.834C>T	p.Asp278Asp	synonymous	Exon 9 of 13	NP_004058.1	P52757-1
	CHN2	NM_001293070.2		c.873C>T	p.Asp291Asp	synonymous	Exon 10 of 14	NP_001279999.1	B7Z1V0
	CHN2	NM_001293072.2		c.789C>T	p.Asp263Asp	synonymous	Exon 9 of 13	NP_001280001.1	B7Z1W9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	ENST00000222792.11	TSL:1 MANE Select	c.834C>T	p.Asp278Asp	synonymous	Exon 9 of 13	ENSP00000222792.7	P52757-1
	CHN2	ENST00000409041.8	TSL:1	c.426C>T	p.Asp142Asp	synonymous	Exon 3 of 5	ENSP00000386849.5	B3VCF5
	CHN2	ENST00000439711.7	TSL:1	c.426C>T	p.Asp142Asp	synonymous	Exon 3 of 5	ENSP00000387425.3	B3VCF6

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

GnomAD2 exomes AF: 0.00122 AC: 304 AN: 249328 AF XY: 0.00105

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 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

African (AFR) AF: 0.000300 AC: 10 AN: 33366

American (AMR) AF: 0.00227 AC: 100 AN: 43996

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 291 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.000572 AC: 49 AN: 85660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00850 AC: 49 AN: 5764

European-Non Finnish (NFE) AF: 0.000410 AC: 455 AN: 1110400

Other (OTH) AF: 0.00181 AC: 109 AN: 60252

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

African (AFR) AF: 0.000121 AC: 5 AN: 41480

American (AMR) AF: 0.00210 AC: 32 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000629 AC: 3 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000736 AC: 50 AN: 67978

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

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

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CHN2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	10
DANN	Benign	0.57
PhyloP100		0.26
Mutation Taster		=95/5	polymorphism

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: rs145906178; hg19: chr7-29539577;