19-9251064-CTTT-C

Variant names:

• chr19-9251064-CTTT-C
• rs201985790
• NM_001079935.2:c.30_32delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001079935.2(OR7E24):​c.30_32delTTT​(p.Phe11del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,054,028 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: OR7E24 NM_001079935.2 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• Publications: 13 publications found

Genes affected

OR7E24 (HGNC:8396): (olfactory receptor family 7 subfamily E member 24) 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001079935.2. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079935.2. 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
	OR7E24	NM_001079935.2	MANE Select	c.30_32delTTT	p.Phe11del	disruptive_inframe_deletion	Exon 1 of 1	NP_001073404.1	Q6IFN5
	OR7E24	NM_001386108.1		c.30-12_30-10delTTT		intron	N/A	NP_001373037.1	A0A2R8Y4Q1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR7E24	ENST00000456448.3	TSL:6 MANE Select	c.30_32delTTT	p.Phe11del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000387523.1	Q6IFN5
	OR7E24	ENST00000641946.1		c.30-12_30-10delTTT		intron	N/A	ENSP00000494223.1	A0A2R8Y4Q1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000206 AC: 14 AN: 67898 AF XY: 0.0000561

Gnomad AFR exome AF: 0.000644

Gnomad AMR exome AF: 0.000371

Gnomad ASJ exome AF: 0.000407

Gnomad EAS exome AF: 0.000202

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000161

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000104 AC: 11 AN: 1054028 Hom.: 0 AF XY: 0.00000763 AC XY: 4 AN XY: 523934

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

African (AFR) AF: 0.0000415 AC: 1 AN: 24114

American (AMR) AF: 0.0000974 AC: 3 AN: 30808

Ashkenazi Jewish (ASJ) AF: 0.0000546 AC: 1 AN: 18302

East Asian (EAS) AF: 0.0000343 AC: 1 AN: 29148

South Asian (SAS) AF: 0.0000161 AC: 1 AN: 62200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4480

European-Non Finnish (NFE) AF: 0.00000374 AC: 3 AN: 803012

Other (OTH) AF: 0.0000230 AC: 1 AN: 43468

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.090

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: rs201985790; hg19: chr19-9361740; COSMIC: COSV71702286;