11-55368743-C-T

Variant names:

• chr11-55368743-C-T
• rs7927370
• NM_001005275.2:c.770C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001005275.2(OR4A15):​c.770C>T​(p.Ala257Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 1,613,406 control chromosomes in the GnomAD database, including 2,678 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.040 (184 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2494 hom.)
• Consequence: OR4A15 NM_001005275.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 31 publications found

Genes affected

OR4A15 (HGNC:15152): (olfactory receptor family 4 subfamily A member 15) 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4A15	NM_001005275.2	c.770C>T	p.Ala257Val	missense_variant	Exon 1 of 1	ENST00000641526.1	NP_001005275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4A15	ENST00000641526.1	c.770C>T	p.Ala257Val	missense_variant	Exon 1 of 1		NM_001005275.2	ENSP00000493060.1

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6144 AN: 152042 Hom.: 184 Cov.: 32

Gnomad AFR AF: 0.00949

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0617

Gnomad OTH AF: 0.0476

GnomAD2 exomes AF: 0.0448 AC: 11236 AN: 250930 AF XY: 0.0461

Gnomad AFR exome AF: 0.00855

Gnomad AMR exome AF: 0.0253

Gnomad ASJ exome AF: 0.0218

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0609

Gnomad NFE exome AF: 0.0634

Gnomad OTH exome AF: 0.0540

GnomAD4 exome AF: 0.0549 AC: 80210 AN: 1461246 Hom.: 2494 Cov.: 33 AF XY: 0.0547 AC XY: 39795 AN XY: 726928

African (AFR) AF: 0.00843 AC: 282 AN: 33466

American (AMR) AF: 0.0255 AC: 1142 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 563 AN: 26124

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39686

South Asian (SAS) AF: 0.0382 AC: 3292 AN: 86234

European-Finnish (FIN) AF: 0.0644 AC: 3439 AN: 53406

Middle Eastern (MID) AF: 0.0330 AC: 190 AN: 5764

European-Non Finnish (NFE) AF: 0.0614 AC: 68211 AN: 1111480

Other (OTH) AF: 0.0511 AC: 3087 AN: 60386

GnomAD4 genome AF: 0.0404 AC: 6143 AN: 152160 Hom.: 184 Cov.: 32 AF XY: 0.0396 AC XY: 2948 AN XY: 74356

African (AFR) AF: 0.00946 AC: 393 AN: 41550

American (AMR) AF: 0.0383 AC: 585 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3470

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5152

South Asian (SAS) AF: 0.0423 AC: 204 AN: 4824

European-Finnish (FIN) AF: 0.0538 AC: 570 AN: 10600

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0617 AC: 4194 AN: 67992

Other (OTH) AF: 0.0471 AC: 99 AN: 2104

Alfa AF: 0.0525 Hom.: 738

Bravo AF: 0.0368

TwinsUK AF: 0.0545 AC: 202

ALSPAC AF: 0.0602 AC: 232

ESP6500AA AF: 0.00909 AC: 40

ESP6500EA AF: 0.0609 AC: 523

ExAC AF: 0.0455 AC: 5521

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.0599

EpiControl AF: 0.0571

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.068
DEOGEN2	Benign	0.0085	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0035	N
LIST_S2	Benign	0.36	T;T
MetaRNN	Benign	0.0030	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.93	N;.
PhyloP100		-1.8
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.8	N;.
REVEL	Benign	0.021
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;.
Polyphen		0.0030	B;.
Vest4		0.017
ClinPred		0.0034	T
GERP RS		-2.0
Varity_R		0.052
gMVP		0.021
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.29		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7927370; hg19: chr11-55136219; COSMIC: COSV107395275;