rs997433

Variant names:

• chr11-5999576-A-G
• rs997433
• NM_001005179.4:c.*2475T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-5999576-A-G
• chr11-5999576-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005179.4(OR56A4):​c.*2475T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,010 control chromosomes in the GnomAD database, including 12,420 homozygotes. 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 0.39 (12420 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: OR56A4 NM_001005179.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660
• Publications: 5 publications found

Genes affected

OR56A4 (HGNC:14791): (olfactory receptor family 56 subfamily A member 4) 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]

OR56A3 (HGNC:14786): (olfactory receptor family 56 subfamily A member 3) 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 (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR56A4	NM_001005179.4	c.*2475T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000641156.1	NP_001005179.3
OR56A3	XM_047426926.1	c.*469-4144A>G		intron_variant	Intron 3 of 5		XP_047282882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR56A4	ENST00000641156.1	c.*2475T>C		3_prime_UTR_variant	Exon 3 of 3		NM_001005179.4	ENSP00000492932.1
OR56A4	ENST00000641835.1	c.*2475T>C		3_prime_UTR_variant	Exon 2 of 2			ENSP00000493371.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59304 AN: 151888 Hom.: 12393 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.391 AC: 59392 AN: 152006 Hom.: 12420 Cov.: 32 AF XY: 0.390 AC XY: 28998 AN XY: 74292

African (AFR) AF: 0.539 AC: 22354 AN: 41462

American (AMR) AF: 0.299 AC: 4573 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1092 AN: 3466

East Asian (EAS) AF: 0.360 AC: 1858 AN: 5168

South Asian (SAS) AF: 0.511 AC: 2464 AN: 4820

European-Finnish (FIN) AF: 0.297 AC: 3136 AN: 10556

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22594 AN: 67940

Other (OTH) AF: 0.392 AC: 827 AN: 2112

Alfa AF: 0.336 Hom.: 10852

Bravo AF: 0.395

Asia WGS AF: 0.475 AC: 1647 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.71
PhyloP100		-0.66

Splicing

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

Other links and lift over

dbSNP: rs997433; hg19: chr11-6020806;