NM_001004701.2:c.262A>T

Variant names:

• chr11-55572389-A-T
• rs370419824
• NM_001004701.2:c.262A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001004701.2(OR4C16):​c.262A>T​(p.Thr88Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,614,012 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T88A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00090 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (40 hom.)
• Consequence: OR4C16 NM_001004701.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 2 publications found

Genes affected

OR4C16 (HGNC:15172): (olfactory receptor family 4 subfamily C member 16) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004136175).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0009 (137/152178) while in subpopulation SAS AF = 0.0276 (133/4814). AF 95% confidence interval is 0.0238. There are 3 homozygotes in GnomAd4. There are 96 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4C16	NM_001004701.2	c.262A>T	p.Thr88Ser	missense_variant	Exon 1 of 1	ENST00000623907.1	NP_001004701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4C16	ENST00000623907.1	c.262A>T	p.Thr88Ser	missense_variant	Exon 1 of 1	6	NM_001004701.2	ENSP00000485295.1

Frequencies

GnomAD3 genomes AF: 0.000901 AC: 137 AN: 152060 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00339 AC: 853 AN: 251390 AF XY: 0.00450

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00157 AC: 2296 AN: 1461834 Hom.: 40 Cov.: 36 AF XY: 0.00230 AC XY: 1674 AN XY: 727228

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0247 AC: 2127 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111960

Other (OTH) AF: 0.00212 AC: 128 AN: 60394

GnomAD4 genome AF: 0.000900 AC: 137 AN: 152178 Hom.: 3 Cov.: 32 AF XY: 0.00129 AC XY: 96 AN XY: 74380

African (AFR) AF: 0.0000241 AC: 1 AN: 41520

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.0276 AC: 133 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000427 Hom.: 0

Bravo AF: 0.000155

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00371 AC: 450

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.019
DANN	Benign	0.71
DEOGEN2	Benign	0.00017	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.19	N
PhyloP100		-1.2
PrimateAI	Benign	0.18	T
Polyphen		0.0010	B
ClinPred		0.017	T
GERP RS		-7.7
PromoterAI		-0.018	Neutral
Varity_R		0.024
gMVP		0.048
Mutation Taster		=100/0	polymorphism

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: rs370419824; hg19: chr11-55339865;