rs9509

chr20-46016514-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004994.3(MMP9):c.*146T>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 0.0703 in 709,702 control chromosomes in the GnomAD database, including 4,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1727 hom., cov: 31)
  • Exomes 𝑓: 0.059 (2483 hom.)
• Consequence: MMP9 NM_004994.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0710

Genes affected

MMP9 (HGNC:7176): (matrix metallopeptidase 9) Proteins of the matrix metalloproteinase (MMP) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The enzyme encoded by this gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling. [provided by RefSeq, Jul 2008]

SLC12A5-AS1 (HGNC:53143): (SLC12A5 and MMP9 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 20-46016514-T-C is Benign according to our data. Variant chr20-46016514-T-C is described in ClinVar as [Benign]. Clinvar id is 338563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP9	NM_004994.3	c.*146T>C		3_prime_UTR_variant	13/13	ENST00000372330.3
SLC12A5-AS1	NR_147699.1	n.669-1726A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP9	ENST00000372330.3	c.*146T>C		3_prime_UTR_variant	13/13	1	NM_004994.3	P1
SLC12A5-AS1	ENST00000535913.2	n.669-1726A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16982 AN: 152042 Hom.: 1724 Cov.: 31

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.0668

Gnomad FIN AF: 0.0282

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0902

GnomAD4 exome AF: 0.0591 AC: 32923 AN: 557542 Hom.: 2483 Cov.: 6 AF XY: 0.0561 AC XY: 16761 AN XY: 299022

Gnomad4 AFR exome AF: 0.256

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.0530

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.0628

Gnomad4 FIN exome AF: 0.0265

Gnomad4 NFE exome AF: 0.0227

Gnomad4 OTH exome AF: 0.0699

GnomAD4 genome AF: 0.112 AC: 17001 AN: 152160 Hom.: 1727 Cov.: 31 AF XY: 0.113 AC XY: 8398 AN XY: 74392

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.0545

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.0668

Gnomad4 FIN AF: 0.0282

Gnomad4 NFE AF: 0.0230

Gnomad4 OTH AF: 0.0897

Alfa AF: 0.0626 Hom.: 327

Bravo AF: 0.130

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Metaphyseal anadysplasia 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	7.2
Dann	Benign	0.89

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: rs9509; hg19: chr20-44645153;