rs17879749

chr11-102796715-CA-Cchr11-102796715-CA-CAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002421.4(MMP1):c.573del(p.Ile191MetfsTer45) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,990 control chromosomes in the GnomAD database, including 183 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.011 (10 hom., cov: 33)
  • Exomes 𝑓: 0.014 (173 hom.)
• Consequence: MMP1 NM_002421.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48

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 11-102796715-CA-C is Benign according to our data. Variant chr11-102796715-CA-C is described in ClinVar as [Benign]. Clinvar id is 2642324.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0112 (1699/152310) while in subpopulation NFE AF= 0.0187 (1269/68024). AF 95% confidence interval is 0.0178. There are 10 homozygotes in gnomad4. There are 798 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP1	NM_002421.4	c.573del	p.Ile191MetfsTer45	frameshift_variant	4/10	ENST00000315274.7
WTAPP1	NR_038390.1	n.584-1307del		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.375del	p.Ile125MetfsTer45	frameshift_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP1	ENST00000315274.7	c.573del	p.Ile191MetfsTer45	frameshift_variant	4/10	1	NM_002421.4	P1
WTAPP1	ENST00000371455.7	n.325-1307del		intron_variant, non_coding_transcript_variant		4
WTAPP1	ENST00000525739.6	n.584-1307del		intron_variant, non_coding_transcript_variant		2
WTAPP1	ENST00000544704.1	n.345-1307del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1699 AN: 152192 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.0114 AC: 2867 AN: 251148 Hom.: 24 AF XY: 0.0119 AC XY: 1610 AN XY: 135726

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.00643

Gnomad ASJ exome AF: 0.00417

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00928

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.0136 AC: 19913 AN: 1461680 Hom.: 173 Cov.: 31 AF XY: 0.0135 AC XY: 9830 AN XY: 727122

Gnomad4 AFR exome AF: 0.00176

Gnomad4 AMR exome AF: 0.00653

Gnomad4 ASJ exome AF: 0.00436

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00966

Gnomad4 FIN exome AF: 0.0125

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.0112 AC: 1699 AN: 152310 Hom.: 10 Cov.: 33 AF XY: 0.0107 AC XY: 798 AN XY: 74480

Gnomad4 AFR AF: 0.00274

Gnomad4 AMR AF: 0.00902

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.0116

Gnomad4 NFE AF: 0.0187

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00508 Hom.: 12

Bravo AF: 0.00973

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0164

EpiControl AF: 0.0141

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

MMP1: BS1, BS2; WTAPP1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs17879749; hg19: chr11-102667446;