chr11-102795242-C-T

Position:

chr11-102795242-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002421.4(MMP1):c.831G>A(p.Ala277=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,613,932 control chromosomes in the GnomAD database, including 715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 49 hom., cov: 33)

Exomes 𝑓: 0.028 ( 666 hom. )

Consequence

MMP1
NM_002421.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.24

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 11-102795242-C-T is Benign according to our data. Variant chr11-102795242-C-T is described in ClinVar as [Benign]. Clinvar id is 403091.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-102795242-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.24 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MMP1	NM_002421.4 linkuse as main transcript	c.831G>A	p.Ala277=	synonymous_variant	6/10	ENST00000315274.7	NP_002412.1
WTAPP1	NR_038390.1 linkuse as main transcript	n.583+18C>T		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2 linkuse as main transcript	c.633G>A	p.Ala211=	synonymous_variant	6/10		NP_001139410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MMP1	ENST00000315274.7 linkuse as main transcript	c.831G>A	p.Ala277=	synonymous_variant	6/10	1	NM_002421.4	ENSP00000322788	P1
WTAPP1	ENST00000371455.7 linkuse as main transcript	n.325-2782C>T		intron_variant, non_coding_transcript_variant		4
WTAPP1	ENST00000525739.6 linkuse as main transcript	n.583+18C>T		intron_variant, non_coding_transcript_variant		2
WTAPP1	ENST00000544704.1 linkuse as main transcript	n.345-2782C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3162

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00734

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.0528

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.00774

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0301

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0209

AC:

5230

AN:

250400

Hom.:

AF XY:

0.0221

AC XY:

2990

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.00771

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.0572

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.00582

Gnomad NFE exome

AF:

0.0294

Gnomad OTH exome

AF:

0.0306

GnomAD4 exome

AF:

0.0277

AC:

40535

AN:

1461668

Hom.:

666

Cov.:

AF XY:

0.0278

AC XY:

20204

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00783

Gnomad4 AMR exome

AF:

0.0173

Gnomad4 ASJ exome

AF:

0.0575

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0111

Gnomad4 FIN exome

AF:

0.00719

Gnomad4 NFE exome

AF:

0.0311

Gnomad4 OTH exome

AF:

0.0280

GnomAD4 genome

AF:

0.0208

AC:

3163

AN:

152264

Hom.:

Cov.:

AF XY:

0.0198

AC XY:

1471

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00736

Gnomad4 AMR

AF:

0.0245

Gnomad4 ASJ

AF:

0.0528

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.00774

Gnomad4 NFE

AF:

0.0301

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0270

Hom.:

Bravo

AF:

0.0210

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0324

EpiControl

AF:

0.0343

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: Silent variant not in splice consensus -

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

-0.58

CADD

Benign

8.1

DANN

Benign

0.61

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