17-78911271-T-C

Variant names:

• chr17-78911271-T-C
• rs6501266
• NM_003255.5:c.130+13688A>G

Variant summary

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

The NM_003255.5(TIMP2):​c.130+13688A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,900 control chromosomes in the GnomAD database, including 24,815 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 0.56 (24815 hom., cov: 30)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• Publications: 15 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]

ENSG00000267491 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 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.130+13688A>G		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.130+13688A>G		intron	N/A	ENSP00000262768.6
	TIMP2	ENST00000536189.6	TSL:2	c.-102+10939A>G		intron	N/A	ENSP00000441724.1
	ENSG00000267491	ENST00000809832.1		n.230-1268T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85666 AN: 151782 Hom.: 24776 Cov.: 30

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.565 AC: 85758 AN: 151900 Hom.: 24815 Cov.: 30 AF XY: 0.561 AC XY: 41623 AN XY: 74252

African (AFR) AF: 0.697 AC: 28868 AN: 41400

American (AMR) AF: 0.494 AC: 7530 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1914 AN: 3468

East Asian (EAS) AF: 0.323 AC: 1667 AN: 5158

South Asian (SAS) AF: 0.396 AC: 1906 AN: 4814

European-Finnish (FIN) AF: 0.562 AC: 5934 AN: 10560

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.531 AC: 36103 AN: 67946

Other (OTH) AF: 0.569 AC: 1199 AN: 2108

Alfa AF: 0.537 Hom.: 90701

Bravo AF: 0.566

Asia WGS AF: 0.357 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.31
PhyloP100		-0.45
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: rs6501266; hg19: chr17-76907353;