17-78913153-A-G

Variant names:

• chr17-78913153-A-G
• rs6416835
• NM_003255.5:c.130+11806T>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.130+11806T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 152,082 control chromosomes in the GnomAD database, including 28,320 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 0.61 (28320 hom., cov: 33)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 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+11806T>C		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+11806T>C		intron	N/A	ENSP00000262768.6
	ENSG00000267491	ENST00000809832.1		n.527A>G		non_coding_transcript_exon	Exon 3 of 3
	TIMP2	ENST00000536189.6	TSL:2	c.-102+9057T>C		intron	N/A	ENSP00000441724.1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92071 AN: 151964 Hom.: 28280 Cov.: 33

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.606 AC: 92162 AN: 152082 Hom.: 28320 Cov.: 33 AF XY: 0.604 AC XY: 44874 AN XY: 74320

African (AFR) AF: 0.703 AC: 29185 AN: 41496

American (AMR) AF: 0.526 AC: 8043 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1996 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2170 AN: 5168

South Asian (SAS) AF: 0.488 AC: 2357 AN: 4826

European-Finnish (FIN) AF: 0.633 AC: 6668 AN: 10538

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39797 AN: 67986

Other (OTH) AF: 0.605 AC: 1276 AN: 2108

Alfa AF: 0.584 Hom.: 31048

Bravo AF: 0.603

Asia WGS AF: 0.446 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.60
PhyloP100		-1.1
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: rs6416835; hg19: chr17-76909235;