rs9905930

Variant names:

• chr17-78863834-C-A
• rs9905930
• NM_003255.5:c.341-6188G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-78863834-C-A
• chr17-78863834-C-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.341-6188G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,116 control chromosomes in the GnomAD database, including 2,031 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 0.16 (2031 hom., cov: 32)
• Consequence: TIMP2 NM_003255.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290
• Publications: 3 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]

ENSG00000305265 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.219 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.341-6188G>T		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.341-6188G>T		intron	N/A	ENSP00000262768.6	P16035
	TIMP2	ENST00000586057.5	TSL:1	c.110-6188G>T		intron	N/A	ENSP00000468296.1	B4DFW2
	TIMP2	ENST00000592761.2	TSL:1	n.428-6188G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23762 AN: 151998 Hom.: 2030 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.156 AC: 23772 AN: 152116 Hom.: 2031 Cov.: 32 AF XY: 0.154 AC XY: 11467 AN XY: 74376

African (AFR) AF: 0.205 AC: 8488 AN: 41480

American (AMR) AF: 0.131 AC: 2002 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3470

East Asian (EAS) AF: 0.185 AC: 951 AN: 5150

South Asian (SAS) AF: 0.231 AC: 1112 AN: 4820

European-Finnish (FIN) AF: 0.123 AC: 1298 AN: 10594

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8994 AN: 68014

Other (OTH) AF: 0.155 AC: 327 AN: 2108

Alfa AF: 0.106 Hom.: 226

Bravo AF: 0.160

Asia WGS AF: 0.218 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.27
PhyloP100		0.29
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: rs9905930; hg19: chr17-76859916;