Variant rs470358 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.105+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,545,902 control chromosomes in the GnomAD database, including 288,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33408 hom., cov: 32)

Exomes 𝑓: 0.60 ( 255473 hom. )

Consequence

MMP1
NM_002421.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0610

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 11-102797971-T-C is Benign according to our data. Variant chr11-102797971-T-C is described in ClinVar as [Benign]. Clinvar id is 1235418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MMP1	NM_002421.4 linkuse as main transcript	c.105+17A>G	intron_variant	ENST00000315274.7	NP_002412.1
WTAPP1	NR_038390.1 linkuse as main transcript	n.584-53T>C	intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2 linkuse as main transcript	c.-53+128A>G	intron_variant		NP_001139410.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
MMP1	ENST00000315274.7 linkuse as main transcript	c.105+17A>G	intron_variant	1	NM_002421.4	ENSP00000322788	P1
WTAPP1	ENST00000371455.7 linkuse as main transcript	n.325-53T>C	intron_variant, non_coding_transcript_variant	4
WTAPP1	ENST00000525739.6 linkuse as main transcript	n.584-53T>C	intron_variant, non_coding_transcript_variant	2
WTAPP1	ENST00000544704.1 linkuse as main transcript	n.345-53T>C	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99685

AN:

151992

Hom.:

33379

Cov.:

show subpopulations

Gnomad AFR

AF:

0.809

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.573

Gnomad ASJ

AF:

0.654

Gnomad EAS

AF:

0.564

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.602

Gnomad OTH

AF:

0.636

GnomAD3 exomes

AF:

0.602

AC:

145180

AN:

240986

Hom.:

44336

AF XY:

0.599

AC XY:

78087

AN XY:

130290

show subpopulations

Gnomad AFR exome

AF:

0.812

Gnomad AMR exome

AF:

0.532

Gnomad ASJ exome

AF:

0.650

Gnomad EAS exome

AF:

0.554

Gnomad SAS exome

AF:

0.570

Gnomad FIN exome

AF:

0.611

Gnomad NFE exome

AF:

0.602

Gnomad OTH exome

AF:

0.619

GnomAD4 exome

AF:

0.603

AC:

840613

AN:

1393792

Hom.:

255473

Cov.:

AF XY:

0.602

AC XY:

419120

AN XY:

696696

show subpopulations

Gnomad4 AFR exome

AF:

0.823

Gnomad4 AMR exome

AF:

0.542

Gnomad4 ASJ exome

AF:

0.647

Gnomad4 EAS exome

AF:

0.611

Gnomad4 SAS exome

AF:

0.564

Gnomad4 FIN exome

AF:

0.613

Gnomad4 NFE exome

AF:

0.600

Gnomad4 OTH exome

AF:

0.607

GnomAD4 genome

AF:

0.656

AC:

99766

AN:

152110

Hom.:

33408

Cov.:

AF XY:

0.652

AC XY:

48509

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.808

Gnomad4 AMR

AF:

0.574

Gnomad4 ASJ

AF:

0.654

Gnomad4 EAS

AF:

0.563

Gnomad4 SAS

AF:

0.584

Gnomad4 FIN

AF:

0.603

Gnomad4 NFE

AF:

0.602

Gnomad4 OTH

AF:

0.639

Alfa

AF:

0.612

Hom.:

28862

Bravo

AF:

0.661

Asia WGS

AF:

0.633

AC:

2200

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.0

DANN

Benign

0.62

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