1-247775603-C-T

Variant names:

• chr1-247775603-C-T
• rs7555046
• ENST00000446393.2:c.694C>T

Variant summary

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

The ENST00000446393.2(OR9H1P):​c.694C>T​(p.Arg232Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 398,534 control chromosomes in the GnomAD database, including 135,000 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 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 0.71 (43322 hom., cov: 31)
  • Exomes 𝑓: 0.86 (91678 hom.)
• Consequence: OR9H1P ENST00000446393.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 2 publications found

Genes affected

OR9H1P (HGNC:15038): (olfactory receptor family 9 subfamily H member 1 pseudogene) 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR9H1	NR_172917.1	n.967C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR9H1P	ENST00000446393.2	c.694C>T	p.Arg232Cys	missense_variant	Exon 2 of 2	6		ENSP00000493452.1
OR9H1P	ENST00000641506.1	n.455C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107611 AN: 152018 Hom.: 43314 Cov.: 31

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.733

GnomAD4 exome AF: 0.855 AC: 210740 AN: 246398 Hom.: 91678 Cov.: 0 AF XY: 0.858 AC XY: 107136 AN XY: 124882

African (AFR) AF: 0.310 AC: 2226 AN: 7180

American (AMR) AF: 0.833 AC: 6193 AN: 7432

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 7079 AN: 9240

East Asian (EAS) AF: 0.973 AC: 22288 AN: 22896

South Asian (SAS) AF: 0.917 AC: 2781 AN: 3032

European-Finnish (FIN) AF: 0.922 AC: 19215 AN: 20850

Middle Eastern (MID) AF: 0.795 AC: 1032 AN: 1298

European-Non Finnish (NFE) AF: 0.865 AC: 136761 AN: 158090

Other (OTH) AF: 0.804 AC: 13165 AN: 16380

GnomAD4 genome AF: 0.708 AC: 107640 AN: 152136 Hom.: 43322 Cov.: 31 AF XY: 0.717 AC XY: 53336 AN XY: 74372

African (AFR) AF: 0.287 AC: 11885 AN: 41440

American (AMR) AF: 0.819 AC: 12518 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2650 AN: 3472

East Asian (EAS) AF: 0.988 AC: 5117 AN: 5180

South Asian (SAS) AF: 0.907 AC: 4371 AN: 4818

European-Finnish (FIN) AF: 0.927 AC: 9844 AN: 10614

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58727 AN: 68020

Other (OTH) AF: 0.736 AC: 1549 AN: 2104

Alfa AF: 0.755 Hom.: 7088

Bravo AF: 0.682

Asia WGS AF: 0.904 AC: 3143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs7555046; hg19: chr1-247938905;