11-5967683-A-G

Variant names:

• chr11-5967683-A-G
• rs141209218
• NM_001146033.1:c.812T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001146033.1(OR56A5):​c.812T>C​(p.Ile271Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00625 in 1,613,878 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I271M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0055 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0063 (44 hom.)
• Consequence: OR56A5 NM_001146033.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.97
• Publications: 4 publications found

Genes affected

OR56A5 (HGNC:14792): (olfactory receptor family 56 subfamily A member 5) 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, Mar 2009]

OR56A3 (HGNC:14786): (olfactory receptor family 56 subfamily A member 3) 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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006551355).
• BP6: Variant 11-5967683-A-G is Benign according to our data. Variant chr11-5967683-A-G is described in ClinVar as Benign. ClinVar VariationId is 2641545.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146033.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR56A5	NM_001146033.1	MANE Select	c.812T>C	p.Ile271Thr	missense	Exon 1 of 1	NP_001139505.1	A0A126GWP3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR56A5	ENST00000532411.2	TSL:6 MANE Select	c.812T>C	p.Ile271Thr	missense	Exon 1 of 1	ENSP00000481594.1	P0C7T3

Frequencies

GnomAD3 genomes AF: 0.00548 AC: 834 AN: 152216 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00591

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00649 AC: 1626 AN: 250678 AF XY: 0.00666

Gnomad AFR exome AF: 0.000865

Gnomad AMR exome AF: 0.00183

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0283

Gnomad NFE exome AF: 0.00736

Gnomad OTH exome AF: 0.00621

GnomAD4 exome AF: 0.00633 AC: 9248 AN: 1461544 Hom.: 44 Cov.: 32 AF XY: 0.00624 AC XY: 4535 AN XY: 726996

African (AFR) AF: 0.000747 AC: 25 AN: 33480

American (AMR) AF: 0.00202 AC: 90 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00203 AC: 175 AN: 86120

European-Finnish (FIN) AF: 0.0281 AC: 1500 AN: 53402

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.00640 AC: 7116 AN: 1111894

Other (OTH) AF: 0.00543 AC: 328 AN: 60392

GnomAD4 genome AF: 0.00547 AC: 833 AN: 152334 Hom.: 7 Cov.: 33 AF XY: 0.00634 AC XY: 472 AN XY: 74488

African (AFR) AF: 0.00106 AC: 44 AN: 41588

American (AMR) AF: 0.00222 AC: 34 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4824

European-Finnish (FIN) AF: 0.0318 AC: 338 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00591 AC: 402 AN: 68026

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00476 Hom.: 1

Bravo AF: 0.00308

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00571 AC: 22

ESP6500AA AF: 0.000723 AC: 1

ESP6500EA AF: 0.00471 AC: 15

ExAC AF: 0.00672 AC: 816

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Benign	0.66
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0066	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.0
PrimateAI	Benign	0.29	T
Sift4G	Uncertain	0.0030	D
Polyphen		0.96	D
Vest4		0.087
MVP		0.22
GERP RS		3.7
Varity_R		0.073
gMVP		0.10

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

Other links and lift over

dbSNP: rs141209218; hg19: chr11-5988913;