17-78874499-C-G

Variant names:

• chr17-78874499-C-G
• rs2009196
• NM_003255.5:c.131-580G>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.131-580G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,058 control chromosomes in the GnomAD database, including 42,523 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 0.75 (42523 hom., cov: 31)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 27 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMP2	NM_003255.5	c.131-580G>C		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.131-580G>C		intron_variant	Intron 1 of 4	1	NM_003255.5	ENSP00000262768.6
TIMP2	ENST00000536189.6	c.-101-580G>C		intron_variant	Intron 1 of 4	2		ENSP00000441724.1
TIMP2	ENST00000586713.6	c.-101-580G>C		intron_variant	Intron 3 of 6	3		ENSP00000465968.2

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113257 AN: 151938 Hom.: 42499 Cov.: 31

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.745 AC: 113335 AN: 152058 Hom.: 42523 Cov.: 31 AF XY: 0.744 AC XY: 55285 AN XY: 74310

African (AFR) AF: 0.734 AC: 30436 AN: 41462

American (AMR) AF: 0.800 AC: 12220 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2863 AN: 3472

East Asian (EAS) AF: 0.545 AC: 2805 AN: 5148

South Asian (SAS) AF: 0.552 AC: 2655 AN: 4814

European-Finnish (FIN) AF: 0.782 AC: 8283 AN: 10586

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

European-Non Finnish (NFE) AF: 0.760 AC: 51683 AN: 67986

Other (OTH) AF: 0.757 AC: 1601 AN: 2116

Alfa AF: 0.699 Hom.: 2104

Bravo AF: 0.748

Asia WGS AF: 0.583 AC: 2027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.41
PhyloP100		0.088
PromoterAI		0.013	Neutral
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: rs2009196; hg19: chr17-76870581;