rs7945189

Variant names:

• chr11-102789833-C-T
• rs7945189
• ENST00000680179.1:n.1167G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000680179.1(MMP1):​n.1167G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 151,300 control chromosomes in the GnomAD database, including 500 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.074 (500 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MMP1 ENST00000680179.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.566
• Publications: 23 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WTAPP1	NR_038390.1	n.390-3312C>T		intron_variant	Intron 1 of 7
MMP1	NM_002421.4	c.*579G>A		downstream_gene_variant		ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.*579G>A		downstream_gene_variant			NP_001139410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.*579G>A		downstream_gene_variant		1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11194 AN: 151182 Hom.: 498 Cov.: 32

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0591

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0688

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0740 AC: 11197 AN: 151300 Hom.: 500 Cov.: 32 AF XY: 0.0735 AC XY: 5430 AN XY: 73866

African (AFR) AF: 0.0250 AC: 1028 AN: 41172

American (AMR) AF: 0.0590 AC: 892 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 270 AN: 3470

East Asian (EAS) AF: 0.0750 AC: 386 AN: 5146

South Asian (SAS) AF: 0.136 AC: 652 AN: 4796

European-Finnish (FIN) AF: 0.0837 AC: 870 AN: 10392

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6839 AN: 67894

Other (OTH) AF: 0.0685 AC: 144 AN: 2102

Alfa AF: 0.0901 Hom.: 2207

Bravo AF: 0.0684

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		-0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7945189; hg19: chr11-102660564;