Variant rs1144391 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002421.4(MMP1):c.900-13T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,602,238 control chromosomes in the GnomAD database, including 94,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7297 hom., cov: 33)

Exomes 𝑓: 0.34 ( 87215 hom. )

Consequence

MMP1
NM_002421.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.148

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:

MMP1 (HGNC:):

MMP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 11-102792751-A-T is Benign according to our data. Variant chr11-102792751-A-T is described in ClinVar as [Benign]. Clinvar id is 403090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MMP1	NM_002421.4 linkuse as main transcript	c.900-13T>A	intron_variant	ENST00000315274.7	NP_002412.1	P03956Q53G95
MMP1	NM_001145938.2 linkuse as main transcript	c.702-13T>A	intron_variant		NP_001139410.1	B4DN15
WTAPP1	NR_038390.1 linkuse as main transcript	n.390-394A>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7 linkuse as main transcript	c.900-13T>A		intron_variant		1	NM_002421.4	ENSP00000322788.6		P03956

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45543

AN:

151872

Hom.:

7300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.0844

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.293

GnomAD3 exomes

AF:

0.301

AC:

74064

AN:

245950

Hom.:

12288

AF XY:

0.309

AC XY:

40920

AN XY:

132592

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.399

Gnomad EAS exome

AF:

0.0808

Gnomad SAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.361

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.342

AC:

496063

AN:

1450248

Hom.:

87215

Cov.:

AF XY:

0.342

AC XY:

246826

AN XY:

720698

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.209

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.115

Gnomad4 SAS exome

AF:

0.317

Gnomad4 FIN exome

AF:

0.310

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.300

AC:

45544

AN:

151990

Hom.:

7297

Cov.:

AF XY:

0.293

AC XY:

21799

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.0840

Gnomad4 SAS

AF:

0.319

Gnomad4 FIN

AF:

0.287

Gnomad4 NFE

AF:

0.364

Gnomad4 OTH

AF:

0.290

Alfa

AF:

0.331

Hom.:

1555

Bravo

AF:

0.291

Asia WGS

AF:

0.224

AC:

777

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.2

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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