dbSNP rs7503726: TIMP2:c.-261A>G (chr17-78925349-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003255.5(TIMP2):c.-261A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 150,754 control chromosomes in the GnomAD database, including 31,103 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 0.64 ( 30948 hom., cov: 30)

Exomes 𝑓: 0.59 ( 155 hom. )

Consequence

TIMP2
NM_003255.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0330

Publications

12 publications found

Variant links:

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]

TIMP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMP2	NM_003255.5 link	c.-261A>G		5_prime_UTR_variant	Exon 1 of 5	ENST00000262768.11	NP_003246.1	P16035A0A140VK57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMP2	ENST00000262768.11 link	c.-261A>G		5_prime_UTR_variant	Exon 1 of 5	1	NM_003255.5	ENSP00000262768.6		P16035

Frequencies

GnomAD3 genomes

AF:

0.639

AC:

95700

AN:

149822

Hom.:

30928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.541

Gnomad AMR

AF:

0.549

Gnomad ASJ

AF:

0.610

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.608

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.732

Gnomad NFE

AF:

0.617

Gnomad OTH

AF:

0.645

GnomAD4 exome

AF:

0.587

AC:

485

AN:

826

Hom.:

155

Cov.:

AF XY:

0.606

AC XY:

241

AN XY:

398

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.585

AC:

466

AN:

796

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.639

AC:

95760

AN:

149928

Hom.:

30948

Cov.:

AF XY:

0.641

AC XY:

46851

AN XY:

73106

show subpopulations

African (AFR)

AF:

0.715

AC:

29459

AN:

41200

American (AMR)

AF:

0.548

AC:

8295

AN:

15124

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

2085

AN:

3418

East Asian (EAS)

AF:

0.531

AC:

2671

AN:

5034

South Asian (SAS)

AF:

0.608

AC:

2915

AN:

4798

European-Finnish (FIN)

AF:

0.689

AC:

6975

AN:

10118

Middle Eastern (MID)

AF:

0.736

AC:

212

AN:

288

European-Non Finnish (NFE)

AF:

0.617

AC:

41315

AN:

66960

Other (OTH)

AF:

0.645

AC:

1343

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1724

3447

5171

6894

8618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.628

Hom.:

3683

Bravo

AF:

0.632

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.1

(source)

DANN

Benign

0.50

PhyloP100

0.033

PromoterAI

0.077

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over