Variant rs17884110 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_002421.4(MMP1):c.900-8_900-7insC variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,605,804 control chromosomes in the GnomAD database, including 94,809 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 7294 hom., cov: 0)

Exomes 𝑓: 0.34 ( 87515 hom. )

Consequence

MMP1
NM_002421.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.776

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 -10 ACMG points.

BP6

Variant 11-102792745-A-AG is Benign according to our data. Variant chr11-102792745-A-AG is described in ClinVar as [Benign]. Clinvar id is 403089.Status of the report is criteria_provided_single_submitter, 1 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
MMP1	NM_002421.4 linkuse as main transcript	c.900-8_900-7insC	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000315274.7	NP_002412.1
WTAPP1	NR_038390.1 linkuse as main transcript	n.390-399dup	intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2 linkuse as main transcript	c.702-8_702-7insC	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		NP_001139410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7 linkuse as main transcript	c.900-8_900-7insC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002421.4	ENSP00000322788	P1
WTAPP1	ENST00000371455.7 linkuse as main transcript	n.325-5278dup		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45532

AN:

151848

Hom.:

7297

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:

0.0843

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.293

GnomAD3 exomes

AF:

0.302

AC:

74610

AN:

247314

Hom.:

12389

AF XY:

0.309

AC XY:

41280

AN XY:

133466

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.0813

Gnomad SAS exome

AF:

0.323

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.361

Gnomad OTH exome

AF:

0.321

GnomAD4 exome

AF:

0.342

AC:

497503

AN:

1453838

Hom.:

87515

Cov.:

AF XY:

0.343

AC XY:

247747

AN XY:

722882

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.115

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.310

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.328

GnomAD4 genome

AF:

0.300

AC:

45533

AN:

151966

Hom.:

7294

Cov.:

AF XY:

0.293

AC XY:

21794

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.0839

Gnomad4 SAS

AF:

0.321

Gnomad4 FIN

AF:

0.287

Gnomad4 NFE

AF:

0.364

Gnomad4 OTH

AF:

0.290

Alfa

AF:

0.337

Hom.:

1837

Bravo

AF:

0.289

Asia WGS

AF:

0.224

AC:

777

AN:

3478

EpiCase

AF:

0.368

EpiControl

AF:

0.355

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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