3-98087607-G-T

Position:

• chr3-98087607-G-T

Variant summary

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

The NM_054106.1(OR5AC2):​c.435G>T​(p.Gln145His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,613,920 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (56 hom.)
• Consequence: OR5AC2 NM_054106.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.07

Genes affected

OR5AC2 (HGNC:15431): (olfactory receptor family 5 subfamily AC member 2) 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034707189).
• BP6: Variant 3-98087607-G-T is Benign according to our data. Variant chr3-98087607-G-T is described in ClinVar as [Benign]. Clinvar id is 780879.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 = 0.0144 (2185/152236) while in subpopulation AFR AF= 0.0475 (1973/41538). AF 95% confidence interval is 0.0458. There are 40 homozygotes in gnomad4. There are 1071 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5AC2	NM_054106.1	c.435G>T	p.Gln145His	missense_variant	1/1	ENST00000358642.2	NP_473447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5AC2	ENST00000358642.2	c.435G>T	p.Gln145His	missense_variant	1/1	6	NM_054106.1	ENSP00000351466.2

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2170 AN: 152118 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00642

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00491 AC: 1220 AN: 248596 Hom.: 27 AF XY: 0.00390 AC XY: 525 AN XY: 134444

Gnomad AFR exome AF: 0.0501

Gnomad AMR exome AF: 0.00405

Gnomad ASJ exome AF: 0.0196

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000422

Gnomad OTH exome AF: 0.00379

GnomAD4 exome AF: 0.00197 AC: 2883 AN: 1461684 Hom.: 56 Cov.: 34 AF XY: 0.00177 AC XY: 1284 AN XY: 727140

Gnomad4 AFR exome AF: 0.0495

Gnomad4 AMR exome AF: 0.00474

Gnomad4 ASJ exome AF: 0.0183

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000171

Gnomad4 OTH exome AF: 0.00525

GnomAD4 genome AF: 0.0144 AC: 2185 AN: 152236 Hom.: 40 Cov.: 32 AF XY: 0.0144 AC XY: 1071 AN XY: 74436

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.00641

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00372 Hom.: 14

Bravo AF: 0.0169

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0424 AC: 187

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.00519 AC: 630

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000415

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.055
DANN	Benign	0.47
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.044
Sift	Benign	0.22	T
Sift4G	Benign	0.54	T
Polyphen		0.0050	B
Vest4		0.14
MutPred		0.28		Loss of stability (P = 0.0306);
MVP		0.12
MPC		0.011
ClinPred		0.0039	T
GERP RS		-2.6
Varity_R		0.11
gMVP		0.080

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: rs76417121; hg19: chr3-97806451;