rs1378738

Variant names:

• chr11-4971052-G-A
• rs1378738
• NM_021801.5:c.-144-17016G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 = 0.789 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP26	NM_021801.5	MANE Select	c.-144-17016G>A		intron	N/A	NP_068573.2	Q9NRE1
	MMP26	NM_001384608.1		c.-152-17218G>A		intron	N/A	NP_001371537.1	A0A8J8YUH5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP26	ENST00000380390.6	TSL:5 MANE Select	c.-144-17016G>A		intron	N/A	ENSP00000369753.1	Q9NRE1
	MMP26	ENST00000300762.2	TSL:1	c.-152-17218G>A		intron	N/A	ENSP00000300762.2	A0A8J8YUH5

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

African (AFR) AF: 0.796 AC: 33021 AN: 41486

American (AMR) AF: 0.587 AC: 8953 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2243 AN: 3470

East Asian (EAS) AF: 0.720 AC: 3719 AN: 5166

South Asian (SAS) AF: 0.717 AC: 3448 AN: 4810

European-Finnish (FIN) AF: 0.617 AC: 6521 AN: 10572

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40298 AN: 67966

Other (OTH) AF: 0.651 AC: 1378 AN: 2116

Alfa AF: 0.612 Hom.: 122696

Bravo AF: 0.665

Asia WGS AF: 0.711 AC: 2475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.77
PhyloP100		-0.55
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: rs1378738; hg19: chr11-4992282;