11-102790934-G-A

Position:

• chr11-102790934-G-A

Variant summary

Our verdict is Benign. Variant got -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

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:44115): (WTAP pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP1	NM_002421.4	c.1197-128C>T		intron_variant		ENST00000315274.7
WTAPP1	NR_038390.1	n.390-2211G>A		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.999-128C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP1	ENST00000315274.7	c.1197-128C>T		intron_variant		1	NM_002421.4	P1
WTAPP1	ENST00000371455.7	n.325-7090G>A		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.358

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.296

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

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.254

Alfa AF: 0.291 Hom.: 5870

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs1938901; hg19: chr11-102661665;