chr11-102796715-CA-C

Variant names:

• chr11-102796715-CA-C
• rs17879749
• NM_002421.4:c.573delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002421.4(MMP1):​c.573delT​(p.Ile191MetfsTer45) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,990 control chromosomes in the GnomAD database, including 183 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.011 (10 hom., cov: 33)
  • Exomes 𝑓: 0.014 (173 hom.)
• Consequence: MMP1 NM_002421.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48
• Publications: 12 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.

• BP6: Variant 11-102796715-CA-C is Benign according to our data. Variant chr11-102796715-CA-C is described in ClinVar as Benign. ClinVar VariationId is 2642324.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0112 (1699/152310) while in subpopulation NFE AF = 0.0187 (1269/68024). AF 95% confidence interval is 0.0178. There are 10 homozygotes in GnomAd4. There are 798 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	NM_002421.4	MANE Select	c.573delT	p.Ile191MetfsTer45	frameshift	Exon 4 of 10	NP_002412.1
	MMP1	NM_001145938.2		c.375delT	p.Ile125MetfsTer45	frameshift	Exon 4 of 10	NP_001139410.1
	WTAPP1	NR_038390.1		n.584-1307delA		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	ENST00000315274.7	TSL:1 MANE Select	c.573delT	p.Ile191MetfsTer45	frameshift	Exon 4 of 10	ENSP00000322788.6
	WTAPP1	ENST00000371455.7	TSL:4	n.325-1307delA		intron	N/A
	WTAPP1	ENST00000525739.6	TSL:2	n.584-1307delA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0112 AC: 1699 AN: 152192 Hom.: 10 Cov.: 33

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.0114 AC: 2867 AN: 251148 AF XY: 0.0119

Gnomad AFR exome AF: 0.00240

Gnomad AMR exome AF: 0.00643

Gnomad ASJ exome AF: 0.00417

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0122

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.0136 AC: 19913 AN: 1461680 Hom.: 173 Cov.: 31 AF XY: 0.0135 AC XY: 9830 AN XY: 727122

African (AFR) AF: 0.00176 AC: 59 AN: 33476

American (AMR) AF: 0.00653 AC: 292 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00436 AC: 114 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00966 AC: 833 AN: 86220

European-Finnish (FIN) AF: 0.0125 AC: 668 AN: 53410

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5766

European-Non Finnish (NFE) AF: 0.0156 AC: 17299 AN: 1111902

Other (OTH) AF: 0.0105 AC: 633 AN: 60390

GnomAD4 genome AF: 0.0112 AC: 1699 AN: 152310 Hom.: 10 Cov.: 33 AF XY: 0.0107 AC XY: 798 AN XY: 74480

African (AFR) AF: 0.00274 AC: 114 AN: 41570

American (AMR) AF: 0.00902 AC: 138 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00725 AC: 35 AN: 4828

European-Finnish (FIN) AF: 0.0116 AC: 123 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0187 AC: 1269 AN: 68024

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00508 Hom.: 12

Bravo AF: 0.00973

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0164

EpiControl AF: 0.0141

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
PhyloP100		-1.5
Mutation Taster		=124/76	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs17879749; hg19: chr11-102667446; COSMIC: COSV59509694;