rs16971783

Variant names:

• chr17-78860571-T-A
• rs16971783
• NM_003255.5:c.341-2925A>T

Variant summary

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

The NM_003255.5(TIMP2):​c.341-2925A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0773 in 152,248 control chromosomes in the GnomAD database, including 877 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 0.077 (877 hom., cov: 33)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMP2	NM_003255.5	MANE Select	c.341-2925A>T		intron	N/A	NP_003246.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMP2	ENST00000262768.11	TSL:1 MANE Select	c.341-2925A>T		intron	N/A	ENSP00000262768.6
	TIMP2	ENST00000586057.5	TSL:1	c.110-2925A>T		intron	N/A	ENSP00000468296.1
	TIMP2	ENST00000592761.2	TSL:1	n.428-2925A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11757 AN: 152130 Hom.: 878 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.0781

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0623

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

GnomAD4 genome AF: 0.0773 AC: 11767 AN: 152248 Hom.: 877 Cov.: 33 AF XY: 0.0783 AC XY: 5829 AN XY: 74434

African (AFR) AF: 0.188 AC: 7817 AN: 41524

American (AMR) AF: 0.0398 AC: 609 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.0784 AC: 406 AN: 5176

South Asian (SAS) AF: 0.171 AC: 823 AN: 4826

European-Finnish (FIN) AF: 0.0303 AC: 322 AN: 10620

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0232 AC: 1575 AN: 68022

Other (OTH) AF: 0.0612 AC: 129 AN: 2108

Alfa AF: 0.0520 Hom.: 56

Bravo AF: 0.0783

Asia WGS AF: 0.119 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.79
PhyloP100		0.098
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: rs16971783; hg19: chr17-76856653;