17-78880892-C-T

Variant names:

• chr17-78880892-C-T
• rs8064344
• NM_003255.5:c.131-6973G>A

Variant summary

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

The NM_003255.5(TIMP2):​c.131-6973G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,168 control chromosomes in the GnomAD database, including 47,762 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 0.79 (47762 hom., cov: 32)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMP2	NM_003255.5	c.131-6973G>A		intron_variant	Intron 1 of 4	ENST00000262768.11	NP_003246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMP2	ENST00000262768.11	c.131-6973G>A		intron_variant	Intron 1 of 4	1	NM_003255.5	ENSP00000262768.6
TIMP2	ENST00000536189.6	c.-101-6973G>A		intron_variant	Intron 1 of 4	2		ENSP00000441724.1
TIMP2	ENST00000586713.6	c.-101-6973G>A		intron_variant	Intron 3 of 6	3		ENSP00000465968.2

Frequencies

GnomAD3 genomes AF: 0.789 AC: 120023 AN: 152050 Hom.: 47739 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.801

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.793

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

GnomAD4 genome AF: 0.789 AC: 120098 AN: 152168 Hom.: 47762 Cov.: 32 AF XY: 0.786 AC XY: 58439 AN XY: 74390

African (AFR) AF: 0.786 AC: 32629 AN: 41532

American (AMR) AF: 0.826 AC: 12636 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2934 AN: 3470

East Asian (EAS) AF: 0.545 AC: 2807 AN: 5154

South Asian (SAS) AF: 0.566 AC: 2724 AN: 4814

European-Finnish (FIN) AF: 0.801 AC: 8482 AN: 10594

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55363 AN: 67990

Other (OTH) AF: 0.789 AC: 1666 AN: 2112

Alfa AF: 0.787 Hom.: 12928

Bravo AF: 0.792

Asia WGS AF: 0.594 AC: 2063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.45
DANN	Benign	0.53
PhyloP100		-0.94
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: rs8064344; hg19: chr17-76876974;