chr14-20060048-G-A

Variant names:

• chr14-20060048-G-A
• rs1958715
• NM_001004717.1:c.4G>A

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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 0.44 (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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004717.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4L1	NM_001004717.1	MANE Select	c.4G>A	p.Asp2Asn	missense	Exon 1 of 1	NP_001004717.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4L1	ENST00000315683.1	TSL:6 MANE Select	c.4G>A	p.Asp2Asn	missense	Exon 1 of 1	ENSP00000319217.1

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

GnomAD2 exomes AF: 0.440 AC: 77638 AN: 176278 AF XY: 0.442

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 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

African (AFR) AF: 0.480 AC: 13984 AN: 29128

American (AMR) AF: 0.553 AC: 15128 AN: 27340

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 7365 AN: 20010

East Asian (EAS) AF: 0.548 AC: 20708 AN: 37758

South Asian (SAS) AF: 0.664 AC: 40518 AN: 60998

European-Finnish (FIN) AF: 0.321 AC: 15931 AN: 49570

Middle Eastern (MID) AF: 0.496 AC: 2549 AN: 5142

European-Non Finnish (NFE) AF: 0.396 AC: 403294 AN: 1017824

Other (OTH) AF: 0.443 AC: 23832 AN: 53832

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

African (AFR) AF: 0.495 AC: 20489 AN: 41404

American (AMR) AF: 0.504 AC: 7666 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3466

East Asian (EAS) AF: 0.571 AC: 2946 AN: 5160

South Asian (SAS) AF: 0.685 AC: 3302 AN: 4818

European-Finnish (FIN) AF: 0.317 AC: 3336 AN: 10528

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26757 AN: 67908

Other (OTH) AF: 0.431 AC: 906 AN: 2104

Alfa AF: 0.416 Hom.: 39949

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 v4.9

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
PhyloP100		-0.15
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
PromoterAI		-0.0038	Neutral
Varity_R		0.094
gMVP		0.050
Mutation Taster		=99/1	polymorphism (auto)

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