Variant rs35231465 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_002424.3(MMP8):c.1348C>T(p.Gln450*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 1,613,238 control chromosomes in the GnomAD database, including 442 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 38 hom., cov: 33)

Exomes 𝑓: 0.021 ( 404 hom. )

Consequence

MMP8
NM_002424.3 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.07

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0154 (2340/152260) while in subpopulation NFE AF= 0.0244 (1662/68010). AF 95% confidence interval is 0.0235. There are 38 homozygotes in gnomad4. There are 1075 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP8	NM_002424.3 link	c.1348C>T	p.Gln450*	stop_gained	10/10	ENST00000236826.8	NP_002415.1	P22894

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MMP8	ENST00000236826.8 link	c.1348C>T	p.Gln450*	stop_gained	10/10	1	NM_002424.3	ENSP00000236826.3	P22894
MMP8	ENST00000438475 link	c.*87C>T		3_prime_UTR_variant	9/9	5		ENSP00000401004.2	H7C1M3
MMP8	ENST00000528662.6 link	n.*1325C>T		non_coding_transcript_exon_variant	12/12	5		ENSP00000431431.2	E9PL87
MMP8	ENST00000528662.6 link	n.*1325C>T		3_prime_UTR_variant	12/12	5		ENSP00000431431.2	E9PL87

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2340

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00490

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0244

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0163

AC:

4086

AN:

250812

Hom.:

AF XY:

0.0165

AC XY:

2236

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.00394

Gnomad AMR exome

AF:

0.0122

Gnomad ASJ exome

AF:

0.0196

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.0163

Gnomad NFE exome

AF:

0.0256

Gnomad OTH exome

AF:

0.0200

GnomAD4 exome

AF:

0.0212

AC:

30974

AN:

1460978

Hom.:

404

Cov.:

AF XY:

0.0207

AC XY:

15051

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.00275

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.0199

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00129

Gnomad4 FIN exome

AF:

0.0174

Gnomad4 NFE exome

AF:

0.0248

Gnomad4 OTH exome

AF:

0.0185

GnomAD4 genome

AF:

0.0154

AC:

2340

AN:

152260

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1075

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00488

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.0202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0130

Gnomad4 NFE

AF:

0.0244

Gnomad4 OTH

AF:

0.0170

Alfa

AF:

0.0225

Hom.:

Bravo

AF:

0.0156

TwinsUK

AF:

0.0259

AC:

ALSPAC

AF:

0.0304

AC:

117

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.0226

AC:

194

ExAC

AF:

0.0161

AC:

1950

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0251

EpiControl

AF:

0.0254

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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 in ESP (all): 214/13004= 1.64% -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Benign

0.73

Eigen

Benign

-0.84

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.095

Vest4

0.67

GERP RS

-2.5

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