dbSNP rs470132: MMP1:c.626-219G>T (chr11-102795826-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002421.4(MMP1):c.626-219G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,078 control chromosomes in the GnomAD database, including 8,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.33 ( 8602 hom., cov: 33)

Consequence

MMP1
NM_002421.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.67

Publications

8 publications found

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:):

WTAPP1 links:

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

WTAPP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

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

BP6

Variant 11-102795826-C-A is Benign according to our data. Variant chr11-102795826-C-A is described in ClinVar as Benign. ClinVar VariationId is 1278000.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4 link	c.626-219G>T	intron_variant	Intron 4 of 9	ENST00000315274.7	NP_002412.1	P03956Q53G95
MMP1	NM_001145938.2 link	c.428-219G>T	intron_variant	Intron 4 of 9		NP_001139410.1	B4DN15
WTAPP1	NR_038390.1 link	n.583+602C>A	intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7 link	c.626-219G>T		intron_variant	Intron 4 of 9	1	NM_002421.4	ENSP00000322788.6		P03956

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50071

AN:

151958

Hom.:

8604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.259

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.0828

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.321

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.329

AC:

50090

AN:

152078

Hom.:

8602

Cov.:

AF XY:

0.322

AC XY:

23945

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.338

AC:

14013

AN:

41448

American (AMR)

AF:

0.259

AC:

3958

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

1397

AN:

3472

East Asian (EAS)

AF:

0.0824

AC:

427

AN:

5184

South Asian (SAS)

AF:

0.317

AC:

1531

AN:

4824

European-Finnish (FIN)

AF:

0.289

AC:

3051

AN:

10552

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.363

AC:

24700

AN:

67994

Other (OTH)

AF:

0.318

AC:

671

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1735

3469

5204

6938

8673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.352

Hom.:

4423

Bravo

AF:

0.325

Asia WGS

AF:

0.224

AC:

779

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 19, 2021

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

0.071

(source)

DANN

Benign

0.77

PhyloP100

-2.7

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over