chr7-29507241-C-T

Variant names:

• chr7-29507241-C-T
• rs148176559
• NM_004067.4:c.1005C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BP7

The NM_004067.4(CHN2):​c.1005C>T​(p.Ala335Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000202 in 1,607,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00090 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: CHN2 NM_004067.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.58
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.111).
• BP6: Variant 7-29507241-C-T is Benign according to our data. Variant chr7-29507241-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3048142.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.59 with no splicing effect.

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.1005C>T	p.Ala335Ala	synonymous	Exon 11 of 13	NP_004058.1	P52757-1
	CHN2	NM_001293070.2		c.1044C>T	p.Ala348Ala	synonymous	Exon 12 of 14	NP_001279999.1	B7Z1V0
	CHN2	NM_001293072.2		c.960C>T	p.Ala320Ala	synonymous	Exon 11 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.1005C>T	p.Ala335Ala	synonymous	Exon 11 of 13	ENSP00000222792.7	P52757-1
	CHN2	ENST00000421775.6	TSL:1	c.423C>T	p.Ala141Ala	synonymous	Exon 4 of 6	ENSP00000394284.2	P52757-5
	CHN2	ENST00000409041.8	TSL:1	c.506-2060C>T		intron	N/A	ENSP00000386849.5	B3VCF5

Frequencies

GnomAD3 genomes AF: 0.000903 AC: 137 AN: 151752 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00303

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000368 AC: 90 AN: 244376 AF XY: 0.000280

Gnomad AFR exome AF: 0.00212

Gnomad AMR exome AF: 0.00118

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000335

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000358

Gnomad OTH exome AF: 0.000846

GnomAD4 exome AF: 0.000128 AC: 187 AN: 1455824 Hom.: 0 Cov.: 31 AF XY: 0.000116 AC XY: 84 AN XY: 723986

African (AFR) AF: 0.00245 AC: 81 AN: 33078

American (AMR) AF: 0.00113 AC: 49 AN: 43490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25922

East Asian (EAS) AF: 0.0000760 AC: 3 AN: 39480

South Asian (SAS) AF: 0.0000355 AC: 3 AN: 84476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5734

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1110152

Other (OTH) AF: 0.000349 AC: 21 AN: 60156

GnomAD4 genome AF: 0.000902 AC: 137 AN: 151870 Hom.: 0 Cov.: 32 AF XY: 0.000836 AC XY: 62 AN XY: 74180

African (AFR) AF: 0.00302 AC: 125 AN: 41418

American (AMR) AF: 0.000262 AC: 4 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10490

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

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67962

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.000715 Hom.: 0

Bravo AF: 0.000895

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.34
CADD	Benign	6.0
DANN	Benign	0.53
PhyloP100		-1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs148176559; hg19: chr7-29546857; COSMIC: COSV108074315; COSMIC: COSV108074315;