rs1378738

chr11-4971052-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021801.5(MMP26):c.-144-17016G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,052 control chromosomes in the GnomAD database, including 33,861 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 0.66 (33861 hom., cov: 32)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

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

Verdict is Benign. Variant got -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 = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP26	NM_021801.5	c.-144-17016G>A		intron_variant		ENST00000380390.6
MMP26	NM_001384608.1	c.-152-17218G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP26	ENST00000380390.6	c.-144-17016G>A		intron_variant		5	NM_021801.5	P1
MMP26	ENST00000300762.2	c.-152-17218G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100259 AN: 151934 Hom.: 33818 Cov.: 32

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.660 AC: 100360 AN: 152052 Hom.: 33861 Cov.: 32 AF XY: 0.660 AC XY: 49058 AN XY: 74312

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.717

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.651

Alfa AF: 0.608 Hom.: 57090

Bravo AF: 0.665

Asia WGS AF: 0.711 AC: 2475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.0
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs1378738; hg19: chr11-4992282;