Variant rs3740938 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The ENST00000236826.8(MMP8):c.873C>T(p.Leu291=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 1,600,928 control chromosomes in the GnomAD database, including 5,870 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 0.067 ( 532 hom., cov: 30)

Exomes 𝑓: 0.074 ( 5338 hom. )

Consequence

MMP8
ENST00000236826.8 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0700

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP7

Synonymous conserved (PhyloP=-0.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP8	NM_002424.3 linkuse as main transcript	c.873C>T	p.Leu291=	synonymous_variant	6/10	ENST00000236826.8	NP_002415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MMP8	ENST00000236826.8 linkuse as main transcript	c.873C>T	p.Leu291=	synonymous_variant	6/10	1	NM_002424.3	ENSP00000236826	P1
MMP8	ENST00000438475.2 linkuse as main transcript	c.801C>T	p.Leu267=	synonymous_variant	6/9	5		ENSP00000401004
MMP8	ENST00000528662.6 linkuse as main transcript	c.*850C>T		3_prime_UTR_variant, NMD_transcript_variant	8/12	5		ENSP00000431431

Frequencies

GnomAD3 genomes

AF:

0.0674

AC:

10159

AN:

150710

Hom.:

523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.0887

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.0756

Gnomad MID

AF:

0.0382

Gnomad NFE

AF:

0.0678

Gnomad OTH

AF:

0.0712

GnomAD3 exomes

AF:

0.0973

AC:

24250

AN:

249108

Hom.:

1712

AF XY:

0.0973

AC XY:

13109

AN XY:

134668

show subpopulations

Gnomad AFR exome

AF:

0.0119

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.0921

Gnomad EAS exome

AF:

0.231

Gnomad SAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.0711

Gnomad NFE exome

AF:

0.0633

Gnomad OTH exome

AF:

0.0891

GnomAD4 exome

AF:

0.0745

AC:

107987

AN:

1450102

Hom.:

5338

Cov.:

AF XY:

0.0764

AC XY:

55116

AN XY:

721526

show subpopulations

Gnomad4 AFR exome

AF:

0.0107

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.0884

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.0733

Gnomad4 NFE exome

AF:

0.0621

Gnomad4 OTH exome

AF:

0.0788

GnomAD4 genome

AF:

0.0675

AC:

10179

AN:

150826

Hom.:

532

Cov.:

AF XY:

0.0706

AC XY:

5200

AN XY:

73610

show subpopulations

Gnomad4 AFR

AF:

0.0127

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.0887

Gnomad4 EAS

AF:

0.241

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.0756

Gnomad4 NFE

AF:

0.0679

Gnomad4 OTH

AF:

0.0733

Alfa

AF:

0.0658

Hom.:

613

Bravo

AF:

0.0663

Asia WGS

AF:

0.176

AC:

612

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.6

DANN

Benign

0.77

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over