NM_002421.4:c.900-8dupC

Variant names:

• chr11-102792745-A-AG
• rs17884110
• NM_002421.4:c.900-8dupC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002421.4(MMP1):​c.900-8dupC variant causes a splice region, 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, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.776

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]

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

ACMG classification

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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4	c.900-8dupC		splice_region_variant, intron_variant	Intron 6 of 9	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.702-8dupC		splice_region_variant, intron_variant	Intron 6 of 9		NP_001139410.1
WTAPP1	NR_038390.1	n.390-399dupG		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.900-8dupC		splice_region_variant, intron_variant	Intron 6 of 9	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45532 AN: 151848 Hom.: 7297 Cov.: 0

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

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.: 31 AF XY: 0.343 AC XY: 247747 AN XY: 722882

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.: 0 AF XY: 0.293 AC XY: 21794 AN XY: 74290

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

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

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

Other links and lift over

dbSNP: rs17884110; hg19: chr11-102663476;