rs8179096

Variant names:

• chr17-78925567-G-A
• rs8179096
• NM_003255.5:c.-479C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-78925567-G-A
• chr17-78925567-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003255.5(TIMP2):​c.-479C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0875 in 151,084 control chromosomes in the GnomAD database, including 765 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 0.088 (765 hom., cov: 31)
• Consequence: TIMP2 NM_003255.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 8 publications found

Genes affected

TIMP2 (HGNC:11821): (TIMP metallopeptidase inhibitor 2) This gene is a member of the TIMP gene family. The proteins encoded by this gene family are natural inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. In addition to an inhibitory role against metalloproteinases, the encoded protein has a unique role among TIMP family members in its ability to directly suppress the proliferation of endothelial cells. As a result, the encoded protein may be critical to the maintenance of tissue homeostasis by suppressing the proliferation of quiescent tissues in response to angiogenic factors, and by inhibiting protease activity in tissues undergoing remodelling of the extracellular matrix. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003255.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMP2	NM_003255.5	MANE Select	c.-479C>T		upstream_gene	N/A	NP_003246.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMP2	ENST00000262768.11	TSL:1 MANE Select	c.-479C>T		upstream_gene	N/A	ENSP00000262768.6

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13213 AN: 150988 Hom.: 762 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.00443

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.0663

Gnomad MID AF: 0.0994

Gnomad NFE AF: 0.0547

Gnomad OTH AF: 0.0846

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

GnomAD4 genome AF: 0.0875 AC: 13224 AN: 151084 Hom.: 765 Cov.: 31 AF XY: 0.0901 AC XY: 6650 AN XY: 73814

African (AFR) AF: 0.145 AC: 5974 AN: 41230

American (AMR) AF: 0.0488 AC: 743 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 200 AN: 3470

East Asian (EAS) AF: 0.143 AC: 714 AN: 5008

South Asian (SAS) AF: 0.206 AC: 976 AN: 4742

European-Finnish (FIN) AF: 0.0663 AC: 694 AN: 10460

Middle Eastern (MID) AF: 0.0966 AC: 28 AN: 290

European-Non Finnish (NFE) AF: 0.0547 AC: 3702 AN: 67660

Other (OTH) AF: 0.0899 AC: 189 AN: 2102

Alfa AF: 0.0700 Hom.: 48

Bravo AF: 0.0850

Asia WGS AF: 0.176 AC: 601 AN: 3406

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.22
PromoterAI		0.026	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8179096; hg19: chr17-76921649;