Variant 17-3216221-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014565.3(OR1A1):c.601C>T(p.Leu201Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,614,078 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 33 hom. )

Consequence

OR1A1
NM_014565.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.02

Variant links:

Genes affected

OR1A1 (HGNC:8179): (olfactory receptor family 1 subfamily A 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]

OR1A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-3216221-C-T is Benign according to our data. Variant chr17-3216221-C-T is described in ClinVar as [Benign]. Clinvar id is 786642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1781/152214) while in subpopulation AFR AF= 0.0402 (1668/41500). AF 95% confidence interval is 0.0386. There are 26 homozygotes in gnomad4. There are 831 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR1A1	NM_014565.3 linkuse as main transcript	c.601C>T	p.Leu201Leu	synonymous_variant	4/4	ENST00000641732.2	NP_055380.2	Q9P1Q5A0A126GWA2
OR1A1	NM_001386104.1 linkuse as main transcript	c.601C>T	p.Leu201Leu	synonymous_variant	2/2		NP_001373033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR1A1	ENST00000641732.2 linkuse as main transcript	c.601C>T	p.Leu201Leu	synonymous_variant	4/4		NM_014565.3	ENSP00000493179.1		Q9P1Q5
OR1A1	ENST00000641322.1 linkuse as main transcript	c.601C>T	p.Leu201Leu	synonymous_variant	2/2			ENSP00000492897.1		Q9P1Q5

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1777

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0402

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00327

AC:

821

AN:

251372

Hom.:

AF XY:

0.00238

AC XY:

324

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.0423

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00139

AC:

2038

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

898

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0459

Gnomad4 AMR exome

AF:

0.00306

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.00310

GnomAD4 genome

AF:

0.0117

AC:

1781

AN:

152214

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

831

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0402

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00503

Hom.:

Bravo

AF:

0.0139

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.38

DANN

Benign

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over