17-78872532-A-G

Variant names:

• chr17-78872532-A-G
• rs9900972
• NM_003255.5:c.231+1287T>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.231+1287T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,064 control chromosomes in the GnomAD database, including 46,574 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 0.78 (46574 hom., cov: 31)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 17 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.811 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.231+1287T>C		intron	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.231+1287T>C		intron	N/A	ENSP00000262768.6
	TIMP2	ENST00000586057.5	TSL:1	c.-1+1287T>C		intron	N/A	ENSP00000468296.1
	TIMP2	ENST00000592761.2	TSL:1	n.318+1287T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118444 AN: 151946 Hom.: 46549 Cov.: 31

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.779 AC: 118515 AN: 152064 Hom.: 46574 Cov.: 31 AF XY: 0.776 AC XY: 57705 AN XY: 74336

African (AFR) AF: 0.747 AC: 30935 AN: 41440

American (AMR) AF: 0.823 AC: 12579 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2938 AN: 3472

East Asian (EAS) AF: 0.547 AC: 2820 AN: 5154

South Asian (SAS) AF: 0.563 AC: 2718 AN: 4828

European-Finnish (FIN) AF: 0.819 AC: 8665 AN: 10586

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55356 AN: 67990

Other (OTH) AF: 0.783 AC: 1651 AN: 2108

Alfa AF: 0.801 Hom.: 93449

Bravo AF: 0.780

Asia WGS AF: 0.594 AC: 2065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.6
DANN	Benign	0.46
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs9900972; hg19: chr17-76868614;