11-102790368-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002421.4(MMP1):c.*44A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,185,778 control chromosomes in the GnomAD database, including 70,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (8955 hom., cov: 33)
  • Exomes 𝑓: 0.34 (61990 hom.)
• Consequence: MMP1 NM_002421.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.215

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-102790368-T-C is Benign according to our data. Variant chr11-102790368-T-C is described in ClinVar as [Benign]. Clinvar id is 1245928.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
MMP1	NM_002421.4	c.*44A>G		3_prime_UTR_variant	10/10	ENST00000315274.7
WTAPP1	NR_038390.1	n.390-2777T>C		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.*44A>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP1	ENST00000315274.7	c.*44A>G		3_prime_UTR_variant	10/10	1	NM_002421.4	P1
WTAPP1	ENST00000371455.7	n.325-7656T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51147 AN: 152012 Hom.: 8951 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.0848

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.324

GnomAD3 exomes AF: 0.313 AC: 66843 AN: 213750 Hom.: 11260 AF XY: 0.317 AC XY: 36433 AN XY: 115008

Gnomad AFR exome AF: 0.356

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.396

Gnomad EAS exome AF: 0.0828

Gnomad SAS exome AF: 0.322

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.364

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.341 AC: 352787 AN: 1033648 Hom.: 61990 Cov.: 13 AF XY: 0.341 AC XY: 180694 AN XY: 529690

Gnomad4 AFR exome AF: 0.362

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.361

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.336 AC: 51178 AN: 152130 Hom.: 8955 Cov.: 33 AF XY: 0.329 AC XY: 24456 AN XY: 74388

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.0844

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.322

Alfa AF: 0.339 Hom.: 6801

Bravo AF: 0.333

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.5
Dann	Benign	0.70

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: rs470215; hg19: chr11-102661099; COSMIC: COSV59512243;