11-4769643-CG-C

Position:

• chr11-4769643-CG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001004752.2(OR51F1):​c.295del​(p.Arg99ValfsTer41) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,603,756 control chromosomes in the GnomAD database, including 49,713 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6945 hom., cov: 20)
  • Exomes 𝑓: 0.23 (42768 hom.)
• Consequence: OR51F1 NM_001004752.2 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.839

Genes affected

OR51F1 (HGNC:15196): (olfactory receptor family 51 subfamily F 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

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 -10 ACMG points.

• BP6: Variant 11-4769643-CG-C is Benign according to our data. Variant chr11-4769643-CG-C is described in ClinVar as [Benign]. Clinvar id is 403275.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR51F1	NM_001004752.2	c.295del	p.Arg99ValfsTer41	frameshift_variant	1/1	ENST00000624103.2
MMP26	NM_021801.5	c.-145+2303del		intron_variant		ENST00000380390.6
MMP26	NM_001384608.1	c.-153+2303del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR51F1	ENST00000624103.2	c.295del	p.Arg99ValfsTer41	frameshift_variant	1/1		NM_001004752.2	P1
MMP26	ENST00000380390.6	c.-145+2303del		intron_variant		5	NM_021801.5	P1
MMP26	ENST00000300762.2	c.-153+2303del		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42465 AN: 151834 Hom.: 6933 Cov.: 20

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0986

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.301

GnomAD3 exomes AF: 0.207 AC: 51645 AN: 249938 Hom.: 6810 AF XY: 0.203 AC XY: 27478 AN XY: 135060

Gnomad AFR exome AF: 0.436

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.0983

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.248

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.230 AC: 333584 AN: 1451804 Hom.: 42768 Cov.: 27 AF XY: 0.226 AC XY: 163425 AN XY: 722640

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.000327

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.280 AC: 42524 AN: 151952 Hom.: 6945 Cov.: 20 AF XY: 0.269 AC XY: 19971 AN XY: 74292

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0987

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.298

Alfa AF: 0.167 Hom.: 488

Bravo AF: 0.299

Asia WGS AF: 0.0760 AC: 266 AN: 3478

EpiCase AF: 0.270

EpiControl AF: 0.278

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 4000/12518=31.95% -

Computational scores

Source: dbNSFP v4.3

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: rs34672924; hg19: chr11-4790873; COSMIC: COSV58578681;