rs3765620

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001304441.2(MMP8):c.-66C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,586,530 control chromosomes in the GnomAD database, including 261,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30389 hom., cov: 33)

Exomes 𝑓: 0.56 ( 230866 hom. )

Consequence

MMP8
NM_001304441.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.684

Variant links:

Genes affected

MMP8 (HGNC:7175): (matrix metallopeptidase 8) This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

MMP8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.8309057E-6).

BP6

Variant 11-102724761-G-A is Benign according to our data. Variant chr11-102724761-G-A is described in ClinVar as [Benign]. Clinvar id is 403100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP8	NM_002424.3 link	c.95C>T	p.Thr32Ile	missense_variant	Exon 1 of 10	ENST00000236826.8	NP_002415.1	P22894

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826.8 link	c.95C>T	p.Thr32Ile	missense_variant	Exon 1 of 10	1	NM_002424.3	ENSP00000236826.3		P22894

Frequencies

GnomAD3 genomes

AF:

0.626

AC:

95189

AN:

151996

Hom.:

30368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.756

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.587

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.633

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.610

Gnomad MID

AF:

0.742

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.635

GnomAD3 exomes

AF:

0.592

AC:

144728

AN:

244278

Hom.:

43548

AF XY:

0.591

AC XY:

78046

AN XY:

132118

show subpopulations

Gnomad AFR exome

AF:

0.761

Gnomad AMR exome

AF:

0.551

Gnomad ASJ exome

AF:

0.613

Gnomad EAS exome

AF:

0.636

Gnomad SAS exome

AF:

0.611

Gnomad FIN exome

AF:

0.598

Gnomad NFE exome

AF:

0.565

Gnomad OTH exome

AF:

0.605

GnomAD4 exome

AF:

0.564

AC:

809126

AN:

1434416

Hom.:

230866

Cov.:

AF XY:

0.565

AC XY:

402936

AN XY:

712980

show subpopulations

Gnomad4 AFR exome

AF:

0.765

Gnomad4 AMR exome

AF:

0.553

Gnomad4 ASJ exome

AF:

0.619

Gnomad4 EAS exome

AF:

0.680

Gnomad4 SAS exome

AF:

0.611

Gnomad4 FIN exome

AF:

0.591

Gnomad4 NFE exome

AF:

0.546

Gnomad4 OTH exome

AF:

0.586

GnomAD4 genome

AF:

0.626

AC:

95245

AN:

152114

Hom.:

30389

Cov.:

AF XY:

0.628

AC XY:

46710

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.756

Gnomad4 AMR

AF:

0.586

Gnomad4 ASJ

AF:

0.607

Gnomad4 EAS

AF:

0.634

Gnomad4 SAS

AF:

0.629

Gnomad4 FIN

AF:

0.610

Gnomad4 NFE

AF:

0.558

Gnomad4 OTH

AF:

0.636

Alfa

AF:

0.577

Hom.:

62793

Bravo

AF:

0.629

TwinsUK

AF:

0.529

AC:

1961

ALSPAC

AF:

0.554

AC:

2136

ESP6500AA

AF:

0.751

AC:

3309

ESP6500EA

AF:

0.557

AC:

4788

ExAC

AF:

0.597

AC:

72457

Asia WGS

AF:

0.662

AC:

2299

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.61

CADD

Benign

4.0

DANN

Benign

0.95

DEOGEN2

Benign

0.028

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00022

LIST_S2

Benign

0.0083

MetaRNN

Benign

0.0000048

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.1

PrimateAI

Benign

0.36

PROVEAN

Benign

2.3

REVEL

Benign

0.052

Sift

Benign

0.27

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.022

MPC

0.041

ClinPred

0.0031

GERP RS

0.96

Varity_R

0.037

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over