chr11-102791409-C-T

Variant names:

• chr11-102791409-C-T
• rs59142365
• NM_002421.4:c.1120G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002421.4(MMP1):​c.1120G>A​(p.Val374Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000581 in 1,614,056 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: MMP1 NM_002421.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.19
• Publications: 6 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00739637).
• BP6: Variant 11-102791409-C-T is Benign according to our data. Variant chr11-102791409-C-T is described in ClinVar as Benign. ClinVar VariationId is 768478.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

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.1120G>A	p.Val374Met	missense	Exon 8 of 10	NP_002412.1	P03956
	MMP1	NM_001145938.2		c.922G>A	p.Val308Met	missense	Exon 8 of 10	NP_001139410.1	B4DN15
	WTAPP1	NR_038390.1		n.390-1736C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	ENST00000315274.7	TSL:1 MANE Select	c.1120G>A	p.Val374Met	missense	Exon 8 of 10	ENSP00000322788.6	P03956
	MMP1	ENST00000680179.1		n.298G>A		non_coding_transcript_exon	Exon 3 of 5
	MMP1	ENST00000681445.1		n.294G>A		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.00312 AC: 475 AN: 152200 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000819 AC: 206 AN: 251414 AF XY: 0.000589

Gnomad AFR exome AF: 0.0111

Gnomad AMR exome AF: 0.000549

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000315 AC: 461 AN: 1461738 Hom.: 0 Cov.: 31 AF XY: 0.000282 AC XY: 205 AN XY: 727170

African (AFR) AF: 0.0108 AC: 360 AN: 33474

American (AMR) AF: 0.000559 AC: 25 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000414 AC: 46 AN: 1111888

Other (OTH) AF: 0.000480 AC: 29 AN: 60394

GnomAD4 genome AF: 0.00313 AC: 476 AN: 152318 Hom.: 3 Cov.: 33 AF XY: 0.00298 AC XY: 222 AN XY: 74478

African (AFR) AF: 0.0112 AC: 465 AN: 41564

American (AMR) AF: 0.000327 AC: 5 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00117 Hom.: 1

Bravo AF: 0.00336

ESP6500AA AF: 0.0116 AC: 51

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000947 AC: 115

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MMP1-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.0074	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.2
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.23
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.024	D
Polyphen		1.0	D
Vest4		0.56
MVP		0.57
MPC		0.042
ClinPred		0.085	T
GERP RS		5.7
Varity_R		0.53
gMVP		0.81
Mutation Taster		=66/34	polymorphism

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: rs59142365; hg19: chr11-102662140;