NM_002421.4:c.1197-220C>T

Variant names:

• chr11-102791026-G-A
• rs17878905
• NM_002421.4:c.1197-220C>T

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.1197-220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0734 in 152,268 control chromosomes in the GnomAD database, including 499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.073 (499 hom., cov: 33)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.32
• Publications: 2 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 11-102791026-G-A is Benign according to our data. Variant chr11-102791026-G-A is described in ClinVar as Benign. ClinVar VariationId is 1260475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	NM_002421.4	MANE Select	c.1197-220C>T		intron	N/A	NP_002412.1	P03956
	MMP1	NM_001145938.2		c.999-220C>T		intron	N/A	NP_001139410.1	B4DN15
	WTAPP1	NR_038390.1		n.390-2119G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	ENST00000315274.7	TSL:1 MANE Select	c.1197-220C>T		intron	N/A	ENSP00000322788.6	P03956
	WTAPP1	ENST00000371455.7	TSL:4	n.325-6998G>A		intron	N/A
	WTAPP1	ENST00000525739.6	TSL:2	n.390-2119G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0734 AC: 11170 AN: 152150 Hom.: 497 Cov.: 33

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0590

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.0747

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0820

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0679

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

GnomAD4 genome AF: 0.0734 AC: 11172 AN: 152268 Hom.: 499 Cov.: 33 AF XY: 0.0730 AC XY: 5434 AN XY: 74454

African (AFR) AF: 0.0247 AC: 1026 AN: 41566

American (AMR) AF: 0.0588 AC: 900 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3472

East Asian (EAS) AF: 0.0749 AC: 389 AN: 5194

South Asian (SAS) AF: 0.135 AC: 652 AN: 4820

European-Finnish (FIN) AF: 0.0820 AC: 870 AN: 10604

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

European-Non Finnish (NFE) AF: 0.100 AC: 6807 AN: 67998

Other (OTH) AF: 0.0677 AC: 143 AN: 2112

Alfa AF: 0.0563 Hom.: 83

Bravo AF: 0.0683

Asia WGS AF: 0.0960 AC: 335 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	5.3
DANN	Benign	0.49
PhyloP100		1.3
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: rs17878905; hg19: chr11-102661757;