rs7116423

Variant names:

• chr11-4759908-T-C
• rs7116423
• NM_021801.5:c.-216-7362T>C

Variant summary

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

The NM_021801.5(MMP26):​c.-216-7362T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 152,180 control chromosomes in the GnomAD database, including 1,565 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 0.079 (1565 hom., cov: 32)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 2 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 = 0.27 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.-216-7362T>C		intron	N/A	NP_068573.2
	MMP26	NM_001384608.1		c.-224-7362T>C		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.-216-7362T>C		intron	N/A	ENSP00000369753.1
	MMP26	ENST00000300762.2	TSL:1	c.-224-7362T>C		intron	N/A	ENSP00000300762.2

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12027 AN: 152062 Hom.: 1559 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.0521

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

GnomAD4 genome AF: 0.0793 AC: 12071 AN: 152180 Hom.: 1565 Cov.: 32 AF XY: 0.0758 AC XY: 5645 AN XY: 74436

African (AFR) AF: 0.274 AC: 11362 AN: 41452

American (AMR) AF: 0.0303 AC: 464 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00143 AC: 97 AN: 68008

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

Alfa AF: 0.0474 Hom.: 111

Bravo AF: 0.0953

Asia WGS AF: 0.0210 AC: 75 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	0.99
DANN	Benign	0.37
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs7116423; hg19: chr11-4781138;