1-158579113-C-T

Position:

• chr1-158579113-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001004477.1(OR10X1):​c.787G>A​(p.Val263Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,613,928 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (49 hom., cov: 30)
  • Exomes 𝑓: 0.0015 (45 hom.)
• Consequence: OR10X1 NM_001004477.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.622

Genes affected

OR10X1 (HGNC:14995): (olfactory receptor family 10 subfamily X 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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003947109).
• BP6: Variant 1-158579113-C-T is Benign according to our data. Variant chr1-158579113-C-T is described in ClinVar as [Benign]. Clinvar id is 788691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1939/152066) while in subpopulation AFR AF= 0.0435 (1803/41456). AF 95% confidence interval is 0.0418. There are 49 homozygotes in gnomad4. There are 923 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10X1	NM_001004477.1	c.787G>A	p.Val263Met	missense_variant	1/1	ENST00000623167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10X1	ENST00000623167.1	c.787G>A	p.Val263Met	missense_variant	1/1		NM_001004477.1	P1

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1936 AN: 151948 Hom.: 49 Cov.: 30

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00290

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00958

GnomAD3 exomes AF: 0.00348 AC: 873 AN: 250876 Hom.: 15 AF XY: 0.00257 AC XY: 349 AN XY: 135552

Gnomad AFR exome AF: 0.0437

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00180

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000353

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00149 AC: 2171 AN: 1461862 Hom.: 45 Cov.: 33 AF XY: 0.00127 AC XY: 927 AN XY: 727236

Gnomad4 AFR exome AF: 0.0430

Gnomad4 AMR exome AF: 0.00206

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.000781

Gnomad4 SAS exome AF: 0.000556

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000283

Gnomad4 OTH exome AF: 0.00358

GnomAD4 genome AF: 0.0128 AC: 1939 AN: 152066 Hom.: 49 Cov.: 30 AF XY: 0.0124 AC XY: 923 AN XY: 74330

Gnomad4 AFR AF: 0.0435

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00948

Alfa AF: 0.00193 Hom.: 8

Bravo AF: 0.0142

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0474 AC: 209

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00428 AC: 520

Asia WGS AF: 0.00318 AC: 12 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0064	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.2	M
MutationTaster	Benign	0.93	N
PrimateAI	Benign	0.31	T
Polyphen		1.0	D
ClinPred		0.073	T
GERP RS		4.8
Varity_R		0.15
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73016227; hg19: chr1-158548903; COSMIC: COSV63767167;