11-4740730-C-T

Variant names:

• chr11-4740730-C-T
• rs10836565
• NM_021801.5:c.-216-26540C>T

Variant summary

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

The NM_021801.5(MMP26):​c.-216-26540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,210 control chromosomes in the GnomAD database, including 7,610 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 0.29 (7610 hom., cov: 31)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451
• Publications: 3 publications found

Genes affected

MMP26 (HGNC:14249): (matrix metallopeptidase 26) 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. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers. [provided by RefSeq, May 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021801.5. 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
	MMP26	NM_021801.5	MANE Select	c.-216-26540C>T		intron	N/A	NP_068573.2
	MMP26	NM_001384608.1		c.-224-26540C>T		intron	N/A	NP_001371537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP26	ENST00000380390.6	TSL:5 MANE Select	c.-216-26540C>T		intron	N/A	ENSP00000369753.1
	MMP26	ENST00000300762.2	TSL:1	c.-224-26540C>T		intron	N/A	ENSP00000300762.2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44269 AN: 151106 Hom.: 7581 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.0622

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.293 AC: 44347 AN: 151210 Hom.: 7610 Cov.: 31 AF XY: 0.282 AC XY: 20827 AN XY: 73886

African (AFR) AF: 0.462 AC: 18996 AN: 41120

American (AMR) AF: 0.247 AC: 3763 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1559 AN: 3470

East Asian (EAS) AF: 0.0619 AC: 319 AN: 5150

South Asian (SAS) AF: 0.176 AC: 843 AN: 4778

European-Finnish (FIN) AF: 0.133 AC: 1375 AN: 10312

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.243 AC: 16470 AN: 67848

Other (OTH) AF: 0.316 AC: 664 AN: 2104

Alfa AF: 0.280 Hom.: 995

Bravo AF: 0.315

Asia WGS AF: 0.158 AC: 553 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.32
PhyloP100		-0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10836565; hg19: chr11-4761960;