chr17-78885621-T-C

Variant names:

• chr17-78885621-T-C
• rs4789939
• NM_003255.5:c.131-11702A>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.131-11702A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,046 control chromosomes in the GnomAD database, including 41,342 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 0.71 (41342 hom., cov: 33)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 26 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 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.131-11702A>G		intron	N/A	NP_003246.1	P16035

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMP2	ENST00000262768.11	TSL:1 MANE Select	c.131-11702A>G		intron	N/A	ENSP00000262768.6	P16035
	TIMP2	ENST00000970519.1		c.131-27975A>G		intron	N/A	ENSP00000640578.1
	TIMP2	ENST00000536189.6	TSL:2	c.-101-11702A>G		intron	N/A	ENSP00000441724.1	B4DFW2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108073 AN: 151928 Hom.: 41335 Cov.: 33

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.735

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

GnomAD4 genome AF: 0.711 AC: 108115 AN: 152046 Hom.: 41342 Cov.: 33 AF XY: 0.716 AC XY: 53208 AN XY: 74340

African (AFR) AF: 0.401 AC: 16599 AN: 41412

American (AMR) AF: 0.811 AC: 12415 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3011 AN: 3472

East Asian (EAS) AF: 0.774 AC: 3982 AN: 5146

South Asian (SAS) AF: 0.732 AC: 3527 AN: 4818

European-Finnish (FIN) AF: 0.883 AC: 9368 AN: 10604

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.834 AC: 56665 AN: 67976

Other (OTH) AF: 0.731 AC: 1544 AN: 2112

Alfa AF: 0.791 Hom.: 154291

Bravo AF: 0.693

Asia WGS AF: 0.728 AC: 2529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.70
DANN	Benign	0.79
PhyloP100		-0.33
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: rs4789939; hg19: chr17-76881703;