rs470747

Variant names:

• chr11-102790864-A-G
• rs470747
• NM_002421.4:c.1197-58T>C

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.1197-58T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 917,102 control chromosomes in the GnomAD database, including 54,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (8909 hom., cov: 32)
  • Exomes 𝑓: 0.34 (45822 hom.)
• Consequence: MMP1 NM_002421.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0980
• Publications: 29 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=-0.82).
• BP6: Variant 11-102790864-A-G is Benign according to our data. Variant chr11-102790864-A-G is described in ClinVar as Benign. ClinVar VariationId is 1182135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP1	NM_002421.4	c.1197-58T>C		intron_variant	Intron 8 of 9	ENST00000315274.7	NP_002412.1
MMP1	NM_001145938.2	c.999-58T>C		intron_variant	Intron 8 of 9		NP_001139410.1
WTAPP1	NR_038390.1	n.390-2281A>G		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.1197-58T>C		intron_variant	Intron 8 of 9	1	NM_002421.4	ENSP00000322788.6

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51034 AN: 151884 Hom.: 8905 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.0846

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.341 AC: 260858 AN: 765100 Hom.: 45822 AF XY: 0.341 AC XY: 137924 AN XY: 404608

African (AFR) AF: 0.368 AC: 7086 AN: 19256

American (AMR) AF: 0.226 AC: 8022 AN: 35486

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 8055 AN: 20444

East Asian (EAS) AF: 0.119 AC: 4292 AN: 36216

South Asian (SAS) AF: 0.318 AC: 21430 AN: 67342

European-Finnish (FIN) AF: 0.311 AC: 15856 AN: 51002

Middle Eastern (MID) AF: 0.332 AC: 1428 AN: 4306

European-Non Finnish (NFE) AF: 0.369 AC: 182273 AN: 494000

Other (OTH) AF: 0.335 AC: 12416 AN: 37048

GnomAD4 genome AF: 0.336 AC: 51065 AN: 152002 Hom.: 8909 Cov.: 32 AF XY: 0.328 AC XY: 24400 AN XY: 74324

African (AFR) AF: 0.359 AC: 14893 AN: 41454

American (AMR) AF: 0.259 AC: 3961 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3470

East Asian (EAS) AF: 0.0842 AC: 436 AN: 5176

South Asian (SAS) AF: 0.320 AC: 1538 AN: 4806

European-Finnish (FIN) AF: 0.288 AC: 3052 AN: 10582

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24796 AN: 67928

Other (OTH) AF: 0.321 AC: 675 AN: 2106

Alfa AF: 0.350 Hom.: 19513

Bravo AF: 0.332

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.75
PhyloP100		-0.098
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: rs470747; hg19: chr11-102661595;