NM_002421.4:c.899+221T>A

Variant names:

• chr11-102794953-A-T
• rs488178
• NM_002421.4:c.899+221T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002421.4(MMP1):​c.899+221T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,260 control chromosomes in the GnomAD database, including 57,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.87 (57316 hom., cov: 33)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.475
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-102794953-A-T is Benign according to our data. Variant chr11-102794953-A-T is described in ClinVar as Benign. ClinVar VariationId is 1280205.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002421.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	NM_002421.4	MANE Select	c.899+221T>A		intron	N/A	NP_002412.1
	MMP1	NM_001145938.2		c.701+221T>A		intron	N/A	NP_001139410.1
	WTAPP1	NR_038390.1		n.507-195A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	ENST00000315274.7	TSL:1 MANE Select	c.899+221T>A		intron	N/A	ENSP00000322788.6
	WTAPP1	ENST00000371455.7	TSL:4	n.325-3071A>T		intron	N/A
	WTAPP1	ENST00000525739.6	TSL:2	n.507-195A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131919 AN: 152142 Hom.: 57268 Cov.: 33

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.867 AC: 132026 AN: 152260 Hom.: 57316 Cov.: 33 AF XY: 0.866 AC XY: 64482 AN XY: 74460

African (AFR) AF: 0.842 AC: 34991 AN: 41536

American (AMR) AF: 0.856 AC: 13092 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3082 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4574 AN: 5178

South Asian (SAS) AF: 0.873 AC: 4218 AN: 4830

European-Finnish (FIN) AF: 0.846 AC: 8966 AN: 10594

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.886 AC: 60298 AN: 68032

Other (OTH) AF: 0.870 AC: 1839 AN: 2114

Alfa AF: 0.869 Hom.: 7161

Bravo AF: 0.865

Asia WGS AF: 0.879 AC: 3057 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.35
PhyloP100		0.47
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: rs488178; hg19: chr11-102665684;