rs1144391

chr11-102792751-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002421.4(MMP1):c.900-13T>A variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.148

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 -14 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 id is 403090.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/exons	MANE	UniProt
MMP1	NM_002421.4	c.900-13T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000315274.7
WTAPP1	NR_038390.1	n.390-394A>T		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.702-13T>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP1	ENST00000315274.7	c.900-13T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002421.4	P1
WTAPP1	ENST00000371455.7	n.325-5273A>T		intron_variant, non_coding_transcript_variant		4

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

GnomAD3 exomes AF: 0.301 AC: 74064 AN: 245950 Hom.: 12288 AF XY: 0.309 AC XY: 40920 AN XY: 132592

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 SAS exome AF: 0.321

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

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.362

Gnomad4 OTH exome AF: 0.328

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

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.0840

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.290

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:1

Revision: criteria provided, single submitter

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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.2
Dann	Benign	0.68

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

LitVar

Other links and lift over

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