11-102790228-A-G

Position:

• chr11-102790228-A-G

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.*184T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 432,802 control chromosomes in the GnomAD database, including 4,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2534 hom., cov: 33)
  • Exomes 𝑓: 0.11 (2243 hom.)
• Consequence: MMP1 NM_002421.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.238

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=-0.82).
• BP6: Variant 11-102790228-A-G is Benign according to our data. Variant chr11-102790228-A-G is described in ClinVar as [Benign]. Clinvar id is 1255299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP1	NM_002421.4	c.*184T>C		3_prime_UTR_variant	10/10	ENST00000315274.7
WTAPP1	NR_038390.1	n.390-2917A>G		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.*184T>C		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP1	ENST00000315274.7	c.*184T>C		3_prime_UTR_variant	10/10	1	NM_002421.4	P1
WTAPP1	ENST00000371455.7	n.325-7796A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23339 AN: 152064 Hom.: 2531 Cov.: 33

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.105 AC: 29551 AN: 280620 Hom.: 2243 Cov.: 4 AF XY: 0.105 AC XY: 15363 AN XY: 146038

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.241

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.0419

Gnomad4 NFE exome AF: 0.0805

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.154 AC: 23365 AN: 152182 Hom.: 2534 Cov.: 33 AF XY: 0.154 AC XY: 11452 AN XY: 74420

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0387

Gnomad4 NFE AF: 0.0795

Gnomad4 OTH AF: 0.171

Alfa AF: 0.101 Hom.: 1085

Bravo AF: 0.172

Asia WGS AF: 0.217 AC: 755 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.55

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: rs2071230; hg19: chr11-102660959;