rs7949235

Positions:

• chr11-4863073-T-A

Variant summary

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

The NM_021801.5(MMP26):​c.-145+95732T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,988 control chromosomes in the GnomAD database, including 10,189 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 0.34 (10189 hom., cov: 32)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528

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]

OR51H1 (HGNC:14833): (olfactory receptor family 51 subfamily H member 1) 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP26	NM_021801.5	c.-145+95732T>A		intron_variant		ENST00000380390.6	NP_068573.2
OR51H1	NR_171273.1	n.39+541A>T		intron_variant, non_coding_transcript_variant
MMP26	NM_001384608.1	c.-153+95732T>A		intron_variant			NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP26	ENST00000380390.6	c.-145+95732T>A		intron_variant		5	NM_021801.5	ENSP00000369753	P1
MMP26	ENST00000300762.2	c.-153+95732T>A		intron_variant		1		ENSP00000300762
OR51H1	ENST00000322059.3	n.39+541A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52040 AN: 151870 Hom.: 10188 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.342 AC: 52047 AN: 151988 Hom.: 10189 Cov.: 32 AF XY: 0.342 AC XY: 25434 AN XY: 74272

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.0660

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.319

Alfa AF: 0.401 Hom.: 1614

Bravo AF: 0.319

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.68

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: rs7949235; hg19: chr11-4884303;