rs470221

Variant names:

• chr11-102794539-T-C
• rs470221
• NM_002421.4:c.899+635A>G

Variant summary

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

The NM_002421.4(MMP1):​c.899+635A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,080 control chromosomes in the GnomAD database, including 45,656 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 0.77 (45656 hom., cov: 31)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4	c.899+635A>G		intron_variant	Intron 6 of 9	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.701+635A>G		intron_variant	Intron 6 of 9		NP_001139410.1
WTAPP1	NR_038390.1	n.507-609T>C		intron_variant	Intron 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.899+635A>G		intron_variant	Intron 6 of 9	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117243 AN: 151962 Hom.: 45635 Cov.: 31

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.771 AC: 117319 AN: 152080 Hom.: 45656 Cov.: 31 AF XY: 0.773 AC XY: 57448 AN XY: 74332

African (AFR) AF: 0.667 AC: 27647 AN: 41466

American (AMR) AF: 0.764 AC: 11679 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2735 AN: 3470

East Asian (EAS) AF: 0.883 AC: 4575 AN: 5182

South Asian (SAS) AF: 0.850 AC: 4087 AN: 4810

European-Finnish (FIN) AF: 0.807 AC: 8541 AN: 10578

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55503 AN: 67974

Other (OTH) AF: 0.771 AC: 1628 AN: 2112

Alfa AF: 0.805 Hom.: 33539

Bravo AF: 0.762

Asia WGS AF: 0.850 AC: 2956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.11
DANN	Benign	0.44
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs470221; hg19: chr11-102665270;