11-4708282-C-T

Variant names:

• chr11-4708282-C-T
• rs1389464
• NM_021801.5:c.-217+3237C>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.-217+3237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,000 control chromosomes in the GnomAD database, including 26,579 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 0.58 (26579 hom., cov: 32)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 0 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP26	NM_021801.5	c.-217+3237C>T		intron_variant	Intron 1 of 7	ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-225+3237C>T		intron_variant	Intron 1 of 7		NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP26	ENST00000380390.6	c.-217+3237C>T		intron_variant	Intron 1 of 7	5	NM_021801.5	ENSP00000369753.1
MMP26	ENST00000300762.2	c.-225+3237C>T		intron_variant	Intron 1 of 7	1		ENSP00000300762.2

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88829 AN: 151882 Hom.: 26550 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.585 AC: 88906 AN: 152000 Hom.: 26579 Cov.: 32 AF XY: 0.576 AC XY: 42795 AN XY: 74246

African (AFR) AF: 0.683 AC: 28336 AN: 41482

American (AMR) AF: 0.544 AC: 8296 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2298 AN: 3472

East Asian (EAS) AF: 0.568 AC: 2927 AN: 5154

South Asian (SAS) AF: 0.523 AC: 2518 AN: 4818

European-Finnish (FIN) AF: 0.391 AC: 4129 AN: 10552

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38458 AN: 67942

Other (OTH) AF: 0.619 AC: 1308 AN: 2112

Alfa AF: 0.566 Hom.: 3084

Bravo AF: 0.603

Asia WGS AF: 0.544 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.17
DANN	Benign	0.48
PhyloP100		-0.39

Splicing

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

Other links and lift over

dbSNP: rs1389464; hg19: chr11-4729512;