chr22-23781540-G-A

Variant names:

• chr22-23781540-G-A
• rs28363665
• NM_005940.5:c.1075+131G>A

Variant summary

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

The NM_005940.5(MMP11):​c.1075+131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 849,898 control chromosomes in the GnomAD database, including 4,508 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 0.12 (2778 hom., cov: 31)
  • Exomes 𝑓: 0.031 (1730 hom.)
• Consequence: MMP11 NM_005940.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 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.1075+131G>A		intron	N/A	NP_005931.2
	MMP11	NR_133013.2		n.1049+131G>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.1075+131G>A		intron	N/A	ENSP00000215743.3
	MMP11	ENST00000492464.1	TSL:2	n.492G>A		non_coding_transcript_exon	Exon 2 of 2
	MMP11	ENST00000434318.1	TSL:5	n.436+131G>A		intron	N/A	ENSP00000412107.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17599 AN: 151920 Hom.: 2765 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0575

Gnomad ASJ AF: 0.0551

Gnomad EAS AF: 0.0257

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.0992

GnomAD4 exome AF: 0.0312 AC: 21792 AN: 697860 Hom.: 1730 Cov.: 9 AF XY: 0.0330 AC XY: 11779 AN XY: 357120

African (AFR) AF: 0.374 AC: 6518 AN: 17434

American (AMR) AF: 0.0438 AC: 1071 AN: 24436

Ashkenazi Jewish (ASJ) AF: 0.0574 AC: 939 AN: 16354

East Asian (EAS) AF: 0.0213 AC: 689 AN: 32330

South Asian (SAS) AF: 0.101 AC: 5396 AN: 53542

European-Finnish (FIN) AF: 0.00355 AC: 114 AN: 32124

Middle Eastern (MID) AF: 0.0578 AC: 167 AN: 2890

European-Non Finnish (NFE) AF: 0.0106 AC: 5128 AN: 484288

Other (OTH) AF: 0.0514 AC: 1770 AN: 34462

GnomAD4 genome AF: 0.116 AC: 17650 AN: 152038 Hom.: 2778 Cov.: 31 AF XY: 0.113 AC XY: 8420 AN XY: 74350

African (AFR) AF: 0.359 AC: 14855 AN: 41384

American (AMR) AF: 0.0574 AC: 878 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0551 AC: 191 AN: 3468

East Asian (EAS) AF: 0.0258 AC: 133 AN: 5158

South Asian (SAS) AF: 0.111 AC: 534 AN: 4802

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10622

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0114 AC: 772 AN: 67998

Other (OTH) AF: 0.0982 AC: 207 AN: 2108

Alfa AF: 0.0320 Hom.: 844

Bravo AF: 0.129

Asia WGS AF: 0.0950 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.9
DANN	Benign	0.39
PhyloP100		-0.56
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: rs28363665; hg19: chr22-24123727;