chr11-102792772-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002421.4(MMP1):c.900-34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,594,966 control chromosomes in the GnomAD database, including 73,860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.31 ( 8105 hom., cov: 32)

Exomes 𝑓: 0.29 ( 65755 hom. )

Consequence

MMP1
NM_002421.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.38

Publications

32 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-102792772-T-C is Benign according to our data. Variant chr11-102792772-T-C is described in ClinVar as Benign. ClinVar VariationId is 1293714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002421.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MMP1	NM_002421.4	MANE Select	c.900-34A>G	intron	N/A	NP_002412.1	P03956
MMP1	NM_001145938.2		c.702-34A>G	intron	N/A	NP_001139410.1	B4DN15
WTAPP1	NR_038390.1		n.390-373T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MMP1	ENST00000315274.7	TSL:1 MANE Select	c.900-34A>G	intron	N/A	ENSP00000322788.6	P03956
MMP1	ENST00000681643.1		n.66A>G	non_coding_transcript_exon	Exon 1 of 4
WTAPP1	ENST00000371455.7	TSL:4	n.325-5252T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

47168

AN:

152010

Hom.:

8079

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.417

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.707

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.228

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.321

GnomAD2 exomes

AF:

0.340

AC:

84245

AN:

247700

AF XY:

0.332

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.470

Gnomad ASJ exome

AF:

0.269

Gnomad EAS exome

AF:

0.708

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.275

Gnomad OTH exome

AF:

0.301

GnomAD4 exome

AF:

0.292

AC:

421589

AN:

1442838

Hom.:

65755

Cov.:

AF XY:

0.292

AC XY:

209692

AN XY:

717266

show subpopulations

African (AFR)

AF:

0.300

AC:

9890

AN:

32988

American (AMR)

AF:

0.460

AC:

20286

AN:

44118

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

6899

AN:

25912

East Asian (EAS)

AF:

0.670

AC:

26515

AN:

39550

South Asian (SAS)

AF:

0.333

AC:

28312

AN:

84940

European-Finnish (FIN)

AF:

0.236

AC:

12532

AN:

53198

Middle Eastern (MID)

AF:

0.295

AC:

1687

AN:

5718

European-Non Finnish (NFE)

AF:

0.271

AC:

297200

AN:

1096706

Other (OTH)

AF:

0.306

AC:

18268

AN:

59708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

13674

27348

41021

54695

68369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10196

20392

30588

40784

50980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.310

AC:

47222

AN:

152128

Hom.:

8105

Cov.:

AF XY:

0.314

AC XY:

23379

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.305

AC:

12643

AN:

41492

American (AMR)

AF:

0.417

AC:

6384

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

905

AN:

3470

East Asian (EAS)

AF:

0.707

AC:

3652

AN:

5166

South Asian (SAS)

AF:

0.349

AC:

1680

AN:

4810

European-Finnish (FIN)

AF:

0.228

AC:

2412

AN:

10578

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.273

AC:

18533

AN:

68004

Other (OTH)

AF:

0.328

AC:

692

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1607

3214

4820

6427

8034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.291

Hom.:

9032

Bravo

AF:

0.325

Asia WGS

AF:

0.495

AC:

1722

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.7

(source)

DANN

Benign

0.44

PhyloP100

1.4

BranchPoint Hunter

0.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over