Genetic Variant NM_002424.3:c.622+138T>A (chr11-102721263-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002424.3(MMP8):c.622+138T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,249,360 control chromosomes in the GnomAD database, including 39,759 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 0.18 ( 3071 hom., cov: 32)

Exomes 𝑓: 0.25 ( 36688 hom. )

Consequence

MMP8
NM_002424.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.557

Publications

8 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP8	NM_002424.3 link	c.622+138T>A		intron_variant	Intron 4 of 9	ENST00000236826.8	NP_002415.1	P22894

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMP8	ENST00000236826.8 link	c.622+138T>A	intron_variant	Intron 4 of 9	1	NM_002424.3	ENSP00000236826.3	P22894
MMP8	ENST00000438475.2 link	c.547+138T>A	intron_variant	Intron 4 of 8	5		ENSP00000401004.2	H7C1M3
MMP8	ENST00000528662.6 link	n.*599+138T>A	intron_variant	Intron 6 of 11	5		ENSP00000431431.2	E9PL87
MMP8	ENST00000533258.5 link	n.*656T>A	downstream_gene_variant		3		ENSP00000437173.1	E9PJB3

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

27130

AN:

151902

Hom.:

3068

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0472

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.183

Gnomad EAS

AF:

0.0915

Gnomad SAS

AF:

0.151

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.174

GnomAD4 exome

AF:

0.251

AC:

275283

AN:

1097340

Hom.:

36688

AF XY:

0.249

AC XY:

134788

AN XY:

541872

show subpopulations

African (AFR)

AF:

0.0365

AC:

887

AN:

24302

American (AMR)

AF:

0.219

AC:

4852

AN:

22132

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

3152

AN:

17822

East Asian (EAS)

AF:

0.0743

AC:

2617

AN:

35204

South Asian (SAS)

AF:

0.169

AC:

9720

AN:

57590

European-Finnish (FIN)

AF:

0.265

AC:

11184

AN:

42252

Middle Eastern (MID)

AF:

0.137

AC:

576

AN:

4216

European-Non Finnish (NFE)

AF:

0.274

AC:

231795

AN:

847276

Other (OTH)

AF:

0.226

AC:

10500

AN:

46546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

9455

18909

28364

37818

47273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7634

15268

22902

30536

38170

<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:

0.178

AC:

27132

AN:

152020

Hom.:

3071

Cov.:

AF XY:

0.177

AC XY:

13157

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0471

AC:

1956

AN:

41504

American (AMR)

AF:

0.198

AC:

3015

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

636

AN:

3468

East Asian (EAS)

AF:

0.0917

AC:

475

AN:

5182

South Asian (SAS)

AF:

0.151

AC:

729

AN:

4814

European-Finnish (FIN)

AF:

0.234

AC:

2467

AN:

10522

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.254

AC:

17243

AN:

67976

Other (OTH)

AF:

0.172

AC:

364

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1078

2156

3234

4312

5390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.212

Hom.:

508

Bravo

AF:

0.173

Asia WGS

AF:

0.105

AC:

364

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.0

(source)

DANN

Benign

0.50

PhyloP100

-0.56

Mutation Taster

=100/0

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