Genetic Variant MMP8:c.903-6C>T (chr11-102715443-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002424.3(MMP8):c.903-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000761 in 1,608,552 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00059 ( 7 hom. )

Consequence

MMP8
NM_002424.3 splice_region, intron

Scores

Splicing: ADA: 0.00002130

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.750

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-102715443-G-A is Benign according to our data. Variant chr11-102715443-G-A is described in ClinVar as [Benign]. Clinvar id is 708208.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP8	NM_002424.3 link	c.903-6C>T		splice_region_variant, intron_variant	Intron 6 of 9	ENST00000236826.8	NP_002415.1	P22894

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMP8	ENST00000236826.8 link	c.903-6C>T	splice_region_variant, intron_variant	Intron 6 of 9	1	NM_002424.3	ENSP00000236826.3	P22894
MMP8	ENST00000438475.2 link	c.828-6C>T	splice_region_variant, intron_variant	Intron 6 of 8	5		ENSP00000401004.2	H7C1M3
MMP8	ENST00000528662.6 link	n.*880-6C>T	splice_region_variant, intron_variant	Intron 8 of 11	5		ENSP00000431431.2	E9PL87

Frequencies

GnomAD3 genomes

AF:

0.00245

AC:

372

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00751

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000853

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000971

AC:

237

AN:

244142

Hom.:

AF XY:

0.000788

AC XY:

104

AN XY:

132038

show subpopulations

Gnomad AFR exome

AF:

0.00818

Gnomad AMR exome

AF:

0.000479

Gnomad ASJ exome

AF:

0.00178

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000511

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000470

Gnomad OTH exome

AF:

0.000838

GnomAD4 exome

AF:

0.000585

AC:

852

AN:

1456376

Hom.:

Cov.:

AF XY:

0.000559

AC XY:

405

AN XY:

724448

show subpopulations

Gnomad4 AFR exome

AF:

0.00803

Gnomad4 AMR exome

AF:

0.000639

Gnomad4 ASJ exome

AF:

0.00171

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000480

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000388

Gnomad4 OTH exome

AF:

0.000615

GnomAD4 genome

AF:

0.00244

AC:

372

AN:

152176

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

184

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00749

Gnomad4 AMR

AF:

0.000852

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.00286

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.52

DANN

Benign

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0

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