Genetic Variant MMP1:c.782-21T>C (chr11-102795312-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_002421.4(MMP1):c.782-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 1,611,958 control chromosomes in the GnomAD database, including 715,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68669 hom., cov: 33)

Exomes 𝑓: 0.94 ( 646356 hom. )

Consequence

MMP1
NM_002421.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.366

Variant links:

Genes affected

MMP1 (HGNC:7155): (matrix metallopeptidase 1) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This secreted protease breaks down the interstitial collagens, including types I, II, and III. The gene is part of a cluster of MMP genes on chromosome 11. Mutations in this gene are associated with chronic obstructive pulmonary disease (COPD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

MMP1 links:

WTAPP1 (HGNC:44115): (WTAP pseudogene 1)

WTAPP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 11-102795312-A-G is Benign according to our data. Variant chr11-102795312-A-G is described in ClinVar as [Benign]. Clinvar id is 1281805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4 link	c.782-21T>C	intron_variant	Intron 5 of 9	ENST00000315274.7	NP_002412.1	P03956Q53G95
MMP1	NM_001145938.2 link	c.584-21T>C	intron_variant	Intron 5 of 9		NP_001139410.1	B4DN15
WTAPP1	NR_038390.1 link	n.583+88A>G	intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MMP1	ENST00000315274.7 link	c.782-21T>C	intron_variant	Intron 5 of 9	1	NM_002421.4	ENSP00000322788.6	P03956
WTAPP1	ENST00000371455.7 link	n.325-2712A>G	intron_variant	Intron 2 of 4	4
WTAPP1	ENST00000525739.6 link	n.583+88A>G	intron_variant	Intron 3 of 7	2
WTAPP1	ENST00000544704.1 link	n.345-2712A>G	intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.949

AC:

144395

AN:

152172

Hom.:

68611

Cov.:

show subpopulations

Gnomad AFR

AF:

0.989

Gnomad AMI

AF:

0.932

Gnomad AMR

AF:

0.903

Gnomad ASJ

AF:

0.921

Gnomad EAS

AF:

0.894

Gnomad SAS

AF:

0.904

Gnomad FIN

AF:

0.917

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.949

Gnomad OTH

AF:

0.939

GnomAD3 exomes

AF:

0.924

AC:

230705

AN:

249776

Hom.:

106860

AF XY:

0.925

AC XY:

124945

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.989

Gnomad AMR exome

AF:

0.844

Gnomad ASJ exome

AF:

0.928

Gnomad EAS exome

AF:

0.885

Gnomad SAS exome

AF:

0.897

Gnomad FIN exome

AF:

0.922

Gnomad NFE exome

AF:

0.952

Gnomad OTH exome

AF:

0.934

GnomAD4 exome

AF:

0.941

AC:

1372997

AN:

1459668

Hom.:

646356

Cov.:

AF XY:

0.940

AC XY:

682378

AN XY:

726276

show subpopulations

Gnomad4 AFR exome

AF:

0.991

Gnomad4 AMR exome

AF:

0.851

Gnomad4 ASJ exome

AF:

0.929

Gnomad4 EAS exome

AF:

0.884

Gnomad4 SAS exome

AF:

0.898

Gnomad4 FIN exome

AF:

0.927

Gnomad4 NFE exome

AF:

0.949

Gnomad4 OTH exome

AF:

0.939

GnomAD4 genome

AF:

0.949

AC:

144512

AN:

152290

Hom.:

68669

Cov.:

AF XY:

0.945

AC XY:

70395

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.989

Gnomad4 AMR

AF:

0.903

Gnomad4 ASJ

AF:

0.921

Gnomad4 EAS

AF:

0.894

Gnomad4 SAS

AF:

0.903

Gnomad4 FIN

AF:

0.917

Gnomad4 NFE

AF:

0.949

Gnomad4 OTH

AF:

0.939

Alfa

AF:

0.947

Hom.:

13755

Bravo

AF:

0.948

Asia WGS

AF:

0.912

AC:

3173

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

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

-0.85

CADD

Benign

5.4

DANN

Benign

0.20

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