NM_002421.4:c.1197-128C>T

Variant names:

• chr11-102790934-G-A
• rs1938901
• NM_002421.4:c.1197-128C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002421.4(MMP1):​c.1197-128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 646,958 control chromosomes in the GnomAD database, including 30,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5892 hom., cov: 33)
  • Exomes 𝑓: 0.31 (24597 hom.)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.108
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-102790934-G-A is Benign according to our data. Variant chr11-102790934-G-A is described in ClinVar as Benign. ClinVar VariationId is 1283938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 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.1197-128C>T		intron	N/A	NP_002412.1
	MMP1	NM_001145938.2		c.999-128C>T		intron	N/A	NP_001139410.1
	WTAPP1	NR_038390.1		n.390-2211G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP1	ENST00000315274.7	TSL:1 MANE Select	c.1197-128C>T		intron	N/A	ENSP00000322788.6
	WTAPP1	ENST00000371455.7	TSL:4	n.325-7090G>A		intron	N/A
	WTAPP1	ENST00000525739.6	TSL:2	n.390-2211G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40539 AN: 151978 Hom.: 5875 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.309 AC: 152965 AN: 494862 Hom.: 24597 AF XY: 0.313 AC XY: 82272 AN XY: 262706

African (AFR) AF: 0.158 AC: 2130 AN: 13490

American (AMR) AF: 0.309 AC: 6925 AN: 22376

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 3219 AN: 14762

East Asian (EAS) AF: 0.465 AC: 14903 AN: 32020

South Asian (SAS) AF: 0.358 AC: 17134 AN: 47902

European-Finnish (FIN) AF: 0.279 AC: 9526 AN: 34166

Middle Eastern (MID) AF: 0.249 AC: 877 AN: 3522

European-Non Finnish (NFE) AF: 0.301 AC: 90021 AN: 298820

Other (OTH) AF: 0.296 AC: 8230 AN: 27804

GnomAD4 genome AF: 0.267 AC: 40584 AN: 152096 Hom.: 5892 Cov.: 33 AF XY: 0.269 AC XY: 20024 AN XY: 74346

African (AFR) AF: 0.160 AC: 6629 AN: 41522

American (AMR) AF: 0.296 AC: 4516 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3468

East Asian (EAS) AF: 0.536 AC: 2769 AN: 5168

South Asian (SAS) AF: 0.361 AC: 1740 AN: 4814

European-Finnish (FIN) AF: 0.277 AC: 2925 AN: 10576

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20419 AN: 67958

Other (OTH) AF: 0.254 AC: 536 AN: 2114

Alfa AF: 0.284 Hom.: 7638

Bravo AF: 0.263

Asia WGS AF: 0.383 AC: 1333 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.43
PhyloP100		-0.11
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: rs1938901; hg19: chr11-102661665;