chr20-46014194-A-C

Variant names:

• chr20-46014194-A-C
• rs13969
• NM_004994.3:c.1821A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004994.3(MMP9):​c.1821A>C​(p.Gly607Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,537,284 control chromosomes in the GnomAD database, including 257,695 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (21915 hom., cov: 33)
  • Exomes 𝑓: 0.58 (235780 hom.)
• Consequence: MMP9 NM_004994.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.24
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 20-46014194-A-C is Benign according to our data. Variant chr20-46014194-A-C is described in ClinVar as Benign. ClinVar VariationId is 285363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004994.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP9	NM_004994.3	MANE Select	c.1821A>C	p.Gly607Gly	synonymous	Exon 11 of 13	NP_004985.2	P14780
	SLC12A5-AS1	NR_147699.1		n.1263T>G		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP9	ENST00000372330.3	TSL:1 MANE Select	c.1821A>C	p.Gly607Gly	synonymous	Exon 11 of 13	ENSP00000361405.3	P14780
	MMP9	ENST00000898203.1		c.1758A>C	p.Gly586Gly	synonymous	Exon 11 of 13	ENSP00000568262.1
	MMP9	ENST00000898204.1		c.1692A>C	p.Gly564Gly	synonymous	Exon 10 of 12	ENSP00000568263.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80229 AN: 151966 Hom.: 21914 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.555

GnomAD2 exomes AF: 0.499 AC: 67779 AN: 135832 AF XY: 0.497

Gnomad AFR exome AF: 0.415

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.565

Gnomad EAS exome AF: 0.246

Gnomad FIN exome AF: 0.533

Gnomad NFE exome AF: 0.606

Gnomad OTH exome AF: 0.543

GnomAD4 exome AF: 0.577 AC: 799523 AN: 1385202 Hom.: 235780 Cov.: 63 AF XY: 0.573 AC XY: 391217 AN XY: 683186

African (AFR) AF: 0.423 AC: 13302 AN: 31436

American (AMR) AF: 0.466 AC: 16507 AN: 35394

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 14180 AN: 25056

East Asian (EAS) AF: 0.239 AC: 8538 AN: 35672

South Asian (SAS) AF: 0.403 AC: 31842 AN: 79006

European-Finnish (FIN) AF: 0.547 AC: 21614 AN: 39494

Middle Eastern (MID) AF: 0.589 AC: 2871 AN: 4878

European-Non Finnish (NFE) AF: 0.611 AC: 658348 AN: 1076632

Other (OTH) AF: 0.561 AC: 32321 AN: 57634

GnomAD4 genome AF: 0.528 AC: 80263 AN: 152082 Hom.: 21915 Cov.: 33 AF XY: 0.521 AC XY: 38745 AN XY: 74348

African (AFR) AF: 0.433 AC: 17978 AN: 41498

American (AMR) AF: 0.542 AC: 8282 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1989 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1227 AN: 5148

South Asian (SAS) AF: 0.387 AC: 1863 AN: 4818

European-Finnish (FIN) AF: 0.540 AC: 5720 AN: 10590

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41276 AN: 67952

Other (OTH) AF: 0.549 AC: 1160 AN: 2112

Alfa AF: 0.530 Hom.: 4186

Bravo AF: 0.520

Asia WGS AF: 0.317 AC: 1107 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Metaphyseal anadysplasia 2 (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13969; hg19: chr20-44642833; COSMIC: COSV63433888;