chr14-18601348-C-T

Variant names:

• chr14-18601348-C-T
• rs1220555775
• NM_001013354.1:c.232C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001013354.1(OR11H12):​c.232C>T​(p.Leu78Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.0000074 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0000063 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR11H12 NM_001013354.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 0 publications found

Genes affected

OR11H12 (HGNC:30738): (olfactory receptor family 11 subfamily H member 12) 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]

ENSG00000306587 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.122 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013354.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR11H12	NM_001013354.1	MANE Select	c.232C>T	p.Leu78Leu	synonymous	Exon 1 of 1	NP_001013372.1	B2RN74

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR11H12	ENST00000550708.2	TSL:6 MANE Select	c.232C>T	p.Leu78Leu	synonymous	Exon 1 of 1	ENSP00000449002.1	B2RN74
	ENSG00000306587	ENST00000819518.1		n.114+11291C>T		intron	N/A
	ENSG00000306587	ENST00000819519.1		n.188+1573C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000736 AC: 1 AN: 135778 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000157

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000634 AC: 9 AN: 1420008 Hom.: 0 Cov.: 31 AF XY: 0.00000848 AC XY: 6 AN XY: 707454

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

African (AFR) AF: 0.00 AC: 0 AN: 30480

American (AMR) AF: 0.00 AC: 0 AN: 44188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25720

East Asian (EAS) AF: 0.00 AC: 0 AN: 39378

South Asian (SAS) AF: 0.00 AC: 0 AN: 85148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53016

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3976

European-Non Finnish (NFE) AF: 0.00000834 AC: 9 AN: 1079412

Other (OTH) AF: 0.00 AC: 0 AN: 58690

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0340507), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000736 AC: 1 AN: 135778 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 66102

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

African (AFR) AF: 0.00 AC: 0 AN: 33286

American (AMR) AF: 0.00 AC: 0 AN: 13814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3284

East Asian (EAS) AF: 0.00 AC: 0 AN: 4644

South Asian (SAS) AF: 0.00 AC: 0 AN: 4368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000157 AC: 1 AN: 63506

Other (OTH) AF: 0.00 AC: 0 AN: 1836

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.0
DANN	Benign	0.44
PhyloP100		0.12
PromoterAI		-0.0060	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1220555775; hg19: chr14-19377825;