rs28363645

Variant names:

• chr22-23779101-G-A
• rs28363645
• NM_005940.5:c.109-86G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-23779101-G-A
• chr22-23779101-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005940.5(MMP11):​c.109-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,092,624 control chromosomes in the GnomAD database, including 813 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.035 (140 hom., cov: 33)
  • Exomes 𝑓: 0.034 (673 hom.)
• Consequence: MMP11 NM_005940.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 3 publications found

Genes affected

MMP11 (HGNC:7157): (matrix metallopeptidase 11) 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. However, the enzyme encoded by this gene is activated intracellularly by furin within the constitutive secretory pathway. Also in contrast to other MMP's, this enzyme cleaves alpha 1-proteinase inhibitor but weakly degrades structural proteins of the extracellular matrix. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005940.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP11	NM_005940.5	MANE Select	c.109-86G>A		intron	N/A	NP_005931.2
	MMP11	NR_133013.2		n.131-86G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP11	ENST00000215743.8	TSL:1 MANE Select	c.109-86G>A		intron	N/A	ENSP00000215743.3
	MMP11	ENST00000428253.1	TSL:4	n.134-86G>A		intron	N/A
	MMP11	ENST00000437086.5	TSL:2	n.109-86G>A		intron	N/A	ENSP00000408070.1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5266 AN: 152188 Hom.: 138 Cov.: 33

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0455

GnomAD4 exome AF: 0.0343 AC: 32207 AN: 940318 Hom.: 673 AF XY: 0.0346 AC XY: 16216 AN XY: 468512

African (AFR) AF: 0.0338 AC: 802 AN: 23746

American (AMR) AF: 0.0180 AC: 526 AN: 29242

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 918 AN: 19090

East Asian (EAS) AF: 0.0874 AC: 2897 AN: 33136

South Asian (SAS) AF: 0.0437 AC: 2708 AN: 62036

European-Finnish (FIN) AF: 0.0247 AC: 780 AN: 31574

Middle Eastern (MID) AF: 0.0916 AC: 431 AN: 4704

European-Non Finnish (NFE) AF: 0.0308 AC: 21356 AN: 694038

Other (OTH) AF: 0.0418 AC: 1789 AN: 42752

GnomAD4 genome AF: 0.0346 AC: 5272 AN: 152306 Hom.: 140 Cov.: 33 AF XY: 0.0351 AC XY: 2613 AN XY: 74474

African (AFR) AF: 0.0342 AC: 1420 AN: 41570

American (AMR) AF: 0.0207 AC: 317 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 182 AN: 3472

East Asian (EAS) AF: 0.115 AC: 596 AN: 5178

South Asian (SAS) AF: 0.0466 AC: 225 AN: 4830

European-Finnish (FIN) AF: 0.0220 AC: 234 AN: 10622

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0319 AC: 2171 AN: 68012

Other (OTH) AF: 0.0445 AC: 94 AN: 2112

Alfa AF: 0.0332 Hom.: 116

Bravo AF: 0.0346

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0050
DANN	Benign	0.36
PhyloP100		-2.7
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: rs28363645; hg19: chr22-24121288;