chr11-4709950-G-A

Variant names:

• chr11-4709950-G-A
• rs4432013
• NM_021801.5:c.-217+4905G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021801.5(MMP26):​c.-217+4905G>A variant causes a intron change. The variant allele was found at a frequency of 0.827 in 456,824 control chromosomes in the GnomAD database, including 157,217 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 0.83 (53239 hom., cov: 32)
  • Exomes 𝑓: 0.82 (103978 hom.)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.34
• 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]

OR51F5P (HGNC:31283): (olfactory receptor family 51 subfamily F member 5 pseudogene) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ENSG00000290647 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.056).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP26	NM_021801.5	c.-217+4905G>A		intron_variant	Intron 1 of 7	ENST00000380390.6	NP_068573.2
OR51F5P		n.4709950G>A		intragenic_variant
MMP26	NM_001384608.1	c.-225+4905G>A		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+4905G>A		intron_variant	Intron 1 of 7	5	NM_021801.5	ENSP00000369753.1
MMP26	ENST00000300762.2	c.-225+4905G>A		intron_variant	Intron 1 of 7	1		ENSP00000300762.2
OR51F5P	ENST00000609912.1	n.382G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000290647	ENST00000641454.1	n.382G>A		non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126893 AN: 152084 Hom.: 53212 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.794

GnomAD2 exomes AF: 0.823 AC: 113252 AN: 137666 AF XY: 0.824

Gnomad AFR exome AF: 0.906

Gnomad AMR exome AF: 0.847

Gnomad ASJ exome AF: 0.767

Gnomad EAS exome AF: 0.737

Gnomad FIN exome AF: 0.911

Gnomad NFE exome AF: 0.789

Gnomad OTH exome AF: 0.793

GnomAD4 exome AF: 0.824 AC: 251048 AN: 304622 Hom.: 103978 Cov.: 0 AF XY: 0.828 AC XY: 143663 AN XY: 173454

African (AFR) AF: 0.902 AC: 7781 AN: 8628

American (AMR) AF: 0.846 AC: 23089 AN: 27282

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 8327 AN: 10790

East Asian (EAS) AF: 0.747 AC: 6882 AN: 9210

South Asian (SAS) AF: 0.890 AC: 53177 AN: 59744

European-Finnish (FIN) AF: 0.904 AC: 11736 AN: 12976

Middle Eastern (MID) AF: 0.785 AC: 2184 AN: 2782

European-Non Finnish (NFE) AF: 0.796 AC: 126472 AN: 158954

Other (OTH) AF: 0.800 AC: 11400 AN: 14256

GnomAD4 genome AF: 0.834 AC: 126970 AN: 152202 Hom.: 53239 Cov.: 32 AF XY: 0.841 AC XY: 62565 AN XY: 74424

African (AFR) AF: 0.899 AC: 37351 AN: 41542

American (AMR) AF: 0.814 AC: 12442 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2678 AN: 3472

East Asian (EAS) AF: 0.758 AC: 3917 AN: 5170

South Asian (SAS) AF: 0.891 AC: 4297 AN: 4820

European-Finnish (FIN) AF: 0.925 AC: 9813 AN: 10608

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53834 AN: 67992

Other (OTH) AF: 0.792 AC: 1670 AN: 2108

Alfa AF: 0.809 Hom.: 81163

Bravo AF: 0.826

Asia WGS AF: 0.833 AC: 2898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		5.3

Splicing

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

Other links and lift over

dbSNP: rs4432013; hg19: chr11-4731180;