22-23774399-G-T

Variant names:

• chr22-23774399-G-T
• rs738789
• NM_005940.5:c.108+1421G>T

Variant summary

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

The NM_005940.5(MMP11):​c.108+1421G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 152,130 control chromosomes in the GnomAD database, including 64,226 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 0.92 (64226 hom., cov: 31)
• Consequence: MMP11 NM_005940.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.741
• Publications: 5 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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.926 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.108+1421G>T		intron	N/A	NP_005931.2
	MMP11	NR_133013.2		n.130+1421G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP11	ENST00000215743.8	TSL:1 MANE Select	c.108+1421G>T		intron	N/A	ENSP00000215743.3
	MMP11	ENST00000872484.1		c.108+1421G>T		intron	N/A	ENSP00000542543.1
	MMP11	ENST00000872487.1		c.108+1421G>T		intron	N/A	ENSP00000542546.1

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139550 AN: 152012 Hom.: 64201 Cov.: 31

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.929

Gnomad OTH AF: 0.915

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.918 AC: 139619 AN: 152130 Hom.: 64226 Cov.: 31 AF XY: 0.915 AC XY: 68040 AN XY: 74352

African (AFR) AF: 0.934 AC: 38760 AN: 41520

American (AMR) AF: 0.907 AC: 13865 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3230 AN: 3470

East Asian (EAS) AF: 0.722 AC: 3726 AN: 5160

South Asian (SAS) AF: 0.826 AC: 3974 AN: 4812

European-Finnish (FIN) AF: 0.941 AC: 9971 AN: 10600

Middle Eastern (MID) AF: 0.966 AC: 282 AN: 292

European-Non Finnish (NFE) AF: 0.929 AC: 63126 AN: 67970

Other (OTH) AF: 0.905 AC: 1912 AN: 2112

Alfa AF: 0.920 Hom.: 94689

Bravo AF: 0.915

Asia WGS AF: 0.786 AC: 2734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.9
DANN	Benign	0.64
PhyloP100		-0.74
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: rs738789; hg19: chr22-24116586;