11-102790349-G-T

Variant names:

• chr11-102790349-G-T
• rs2239008
• NM_002421.4:c.*63C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002421.4(MMP1):​c.*63C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMP1 NM_002421.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 16 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4	c.*63C>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.*63C>A		3_prime_UTR_variant	Exon 10 of 10		NP_001139410.1
WTAPP1	NR_038390.1	n.390-2796G>T		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.*63C>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 788412 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 410744

African (AFR) AF: 0.00 AC: 0 AN: 19432

American (AMR) AF: 0.00 AC: 0 AN: 30010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18662

East Asian (EAS) AF: 0.00 AC: 0 AN: 35908

South Asian (SAS) AF: 0.00 AC: 0 AN: 58466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2966

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 535664

Other (OTH) AF: 0.00 AC: 0 AN: 37428

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.95
DANN	Benign	0.58
PhyloP100		0.084

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

Other links and lift over

dbSNP: rs2239008; hg19: chr11-102661080;