11-102790143-G-A

Position:

• chr11-102790143-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.*269C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 248,880 control chromosomes in the GnomAD database, including 12,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7104 hom., cov: 32)
  • Exomes 𝑓: 0.32 (5435 hom.)
• Consequence: MMP1 NM_002421.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.667

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=-0.8).
• BP6: Variant 11-102790143-G-A is Benign according to our data. Variant chr11-102790143-G-A is described in ClinVar as [Benign]. Clinvar id is 1267876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP1	NM_002421.4	c.*269C>T		3_prime_UTR_variant	10/10	ENST00000315274.7	NP_002412.1
WTAPP1	NR_038390.1	n.390-3002G>A		intron_variant, non_coding_transcript_variant
MMP1	NM_001145938.2	c.*269C>T		3_prime_UTR_variant	10/10		NP_001139410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP1	ENST00000315274.7	c.*269C>T		3_prime_UTR_variant	10/10	1	NM_002421.4	ENSP00000322788	P1
WTAPP1	ENST00000371455.7	n.325-7881G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44596 AN: 151810 Hom.: 7109 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.0843

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.323 AC: 31293 AN: 96954 Hom.: 5435 Cov.: 0 AF XY: 0.321 AC XY: 16061 AN XY: 50080

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.294 AC: 44592 AN: 151926 Hom.: 7104 Cov.: 32 AF XY: 0.287 AC XY: 21327 AN XY: 74254

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.0839

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.285

Alfa AF: 0.329 Hom.: 2696

Bravo AF: 0.283

Asia WGS AF: 0.220 AC: 764 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	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.75

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: rs5854; hg19: chr11-102660874;