NM_002421.4:c.900-13T>A

Variant names:

• chr11-102792751-A-T
• rs1144391
• NM_002421.4:c.900-13T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002421.4(MMP1):​c.900-13T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,602,238 control chromosomes in the GnomAD database, including 94,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7297 hom., cov: 33)
  • Exomes 𝑓: 0.34 (87215 hom.)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.148
• Publications: 3 publications found

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:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-102792751-A-T is Benign according to our data. Variant chr11-102792751-A-T is described in ClinVar as Benign. ClinVar VariationId is 403090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.900-13T>A		intron_variant	Intron 6 of 9	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.702-13T>A		intron_variant	Intron 6 of 9		NP_001139410.1
WTAPP1	NR_038390.1	n.390-394A>T		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.900-13T>A		intron_variant	Intron 6 of 9	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45543 AN: 151872 Hom.: 7300 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.0844

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.293

GnomAD2 exomes AF: 0.301 AC: 74064 AN: 245950 AF XY: 0.309

Gnomad AFR exome AF: 0.228

Gnomad AMR exome AF: 0.204

Gnomad ASJ exome AF: 0.399

Gnomad EAS exome AF: 0.0808

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.361

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.342 AC: 496063 AN: 1450248 Hom.: 87215 Cov.: 31 AF XY: 0.342 AC XY: 246826 AN XY: 720698

African (AFR) AF: 0.233 AC: 7718 AN: 33140

American (AMR) AF: 0.209 AC: 9165 AN: 43792

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 10314 AN: 25918

East Asian (EAS) AF: 0.115 AC: 4559 AN: 39608

South Asian (SAS) AF: 0.317 AC: 26765 AN: 84308

European-Finnish (FIN) AF: 0.310 AC: 16506 AN: 53326

Middle Eastern (MID) AF: 0.320 AC: 1835 AN: 5738

European-Non Finnish (NFE) AF: 0.362 AC: 399547 AN: 1104418

Other (OTH) AF: 0.328 AC: 19654 AN: 60000

GnomAD4 genome AF: 0.300 AC: 45544 AN: 151990 Hom.: 7297 Cov.: 33 AF XY: 0.293 AC XY: 21799 AN XY: 74304

African (AFR) AF: 0.236 AC: 9786 AN: 41470

American (AMR) AF: 0.242 AC: 3704 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1390 AN: 3464

East Asian (EAS) AF: 0.0840 AC: 435 AN: 5180

South Asian (SAS) AF: 0.319 AC: 1539 AN: 4818

European-Finnish (FIN) AF: 0.287 AC: 3033 AN: 10554

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.364 AC: 24712 AN: 67918

Other (OTH) AF: 0.290 AC: 612 AN: 2110

Alfa AF: 0.331 Hom.: 1555

Bravo AF: 0.291

Asia WGS AF: 0.224 AC: 777 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1144391; hg19: chr11-102663482; COSMIC: COSV59511955;