11-55343596-C-T

Variant names:

• chr11-55343596-C-T
• rs76425968
• NM_001005274.1:c.396C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001005274.1(OR4A16):​c.396C>T​(p.Asn132Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,528,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0092 (0 hom.)
• Consequence: OR4A16 NM_001005274.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15
• Publications: 5 publications found

Genes affected

OR4A16 (HGNC:15153): (olfactory receptor family 4 subfamily A 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Variant has high frequency in the SAS (0.0118) population. However there is too low homozygotes in high coverage region: (expected more than 54, got 0).
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-3.15 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4A16	NM_001005274.1	c.396C>T	p.Asn132Asn	synonymous_variant	Exon 1 of 1	ENST00000314721.5	NP_001005274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4A16	ENST00000314721.5	c.396C>T	p.Asn132Asn	synonymous_variant	Exon 1 of 1	6	NM_001005274.1	ENSP00000325128.2

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5698 AN: 151502 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00947

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.0368

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0573

Gnomad OTH AF: 0.0476

GnomAD2 exomes AF: 0.0000368 AC: 9 AN: 244830 AF XY: 0.0000151

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000949

Gnomad NFE exome AF: 0.0000367

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.00916 AC: 12615 AN: 1376726 Hom.: 0 Cov.: 33 AF XY: 0.0100 AC XY: 6867 AN XY: 684914

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00124 AC: 41 AN: 33086

American (AMR) AF: 0.00654 AC: 282 AN: 43138

Ashkenazi Jewish (ASJ) AF: 0.00437 AC: 111 AN: 25386

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0124 AC: 1025 AN: 82534

European-Finnish (FIN) AF: 0.0222 AC: 1092 AN: 49196

Middle Eastern (MID) AF: 0.0116 AC: 65 AN: 5602

European-Non Finnish (NFE) AF: 0.00900 AC: 9368 AN: 1041010

Other (OTH) AF: 0.0110 AC: 631 AN: 57110

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0376 AC: 5697 AN: 151618 Hom.: 0 Cov.: 33 AF XY: 0.0369 AC XY: 2736 AN XY: 74108

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00947 AC: 393 AN: 41500

American (AMR) AF: 0.0354 AC: 538 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 74 AN: 3464

East Asian (EAS) AF: 0.000583 AC: 3 AN: 5150

South Asian (SAS) AF: 0.0369 AC: 176 AN: 4772

European-Finnish (FIN) AF: 0.0498 AC: 526 AN: 10556

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0573 AC: 3875 AN: 67648

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00664 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.0
DANN	Benign	0.59
PhyloP100		-3.1
PromoterAI		-0.017	Neutral
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: rs76425968; hg19: chr11-55111072; COSMIC: COSV108123261;