rs1958715

Positions:

• chr14-20060048-G-A
• chr14-20060048-G-C
• chr14-20060048-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004717.1(OR4L1):​c.4G>A​(p.Asp2Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,453,402 control chromosomes in the GnomAD database, including 132,996 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.44 (15318 hom., cov: 31)
  • Exomes 𝑓: 0.42 (117678 hom.)
• Consequence: OR4L1 NM_001004717.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

Genes affected

OR4L1 (HGNC:15356): (olfactory receptor family 4 subfamily L 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.7599272E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR4L1	NM_001004717.1	c.4G>A	p.Asp2Asn	missense_variant	1/1	ENST00000315683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4L1	ENST00000315683.1	c.4G>A	p.Asp2Asn	missense_variant	1/1		NM_001004717.1	P1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67015 AN: 151682 Hom.: 15285 Cov.: 31

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.428

GnomAD3 exomes AF: 0.440 AC: 77638 AN: 176278 Hom.: 18247 AF XY: 0.442 AC XY: 41213 AN XY: 93290

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.566

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.567

Gnomad SAS exome AF: 0.668

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.429

GnomAD4 exome AF: 0.417 AC: 543309 AN: 1301602 Hom.: 117678 Cov.: 21 AF XY: 0.423 AC XY: 270671 AN XY: 640102

Gnomad4 AFR exome AF: 0.480

Gnomad4 AMR exome AF: 0.553

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.548

Gnomad4 SAS exome AF: 0.664

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.442 AC: 67105 AN: 151800 Hom.: 15318 Cov.: 31 AF XY: 0.445 AC XY: 33006 AN XY: 74178

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.431

Alfa AF: 0.410 Hom.: 27425

Bravo AF: 0.453

TwinsUK AF: 0.415 AC: 1537

ALSPAC AF: 0.422 AC: 1628

ESP6500AA AF: 0.487 AC: 2146

ESP6500EA AF: 0.402 AC: 3457

ExAC AF: 0.456 AC: 54436

Asia WGS AF: 0.614 AC: 2135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0000028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.97	P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.061
Sift	Benign	0.17	T
Sift4G	Benign	0.23	T
Polyphen		0.0020	B
Vest4		0.040
MPC		0.011
ClinPred		0.0053	T
GERP RS		1.4
Varity_R		0.094
gMVP		0.050

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

Publications

LitVar

Other links and lift over

dbSNP: rs1958715; hg19: chr14-20528207; COSMIC: COSV59850389;