19-9251064-CTTT-CTTTT

Variant names:

• chr19-9251064-C-CT
• rs201985790
• NM_001079935.2:c.32dupT

Variant summary

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

The NM_001079935.2(OR7E24):​c.32dupT​(p.Leu12ProfsTer59) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 948,930 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1 hom.)
• Consequence: OR7E24 NM_001079935.2 frameshift
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.465
• 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 0 ACMG points.

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.32dupT	p.Leu12ProfsTer59	frameshift	Exon 1 of 1	NP_001073404.1	Q6IFN5
	OR7E24	NM_001386108.1		c.30-10dupT		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.32dupT	p.Leu12ProfsTer59	frameshift	Exon 1 of 1	ENSP00000387523.1	Q6IFN5
	OR7E24	ENST00000641946.1		c.30-10dupT		intron	N/A	ENSP00000494223.1	A0A2R8Y4Q1

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 234 AN: 147770 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00456

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000474

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00176

Gnomad SAS AF: 0.000640

Gnomad FIN AF: 0.00124

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000225

Gnomad OTH AF: 0.00199

GnomAD2 exomes AF: 0.0917 AC: 6228 AN: 67898 AF XY: 0.0972

Gnomad AFR exome AF: 0.0619

Gnomad AMR exome AF: 0.112

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.0752

Gnomad FIN exome AF: 0.0552

Gnomad NFE exome AF: 0.0844

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.0462 AC: 37024 AN: 801080 Hom.: 1 Cov.: 30 AF XY: 0.0455 AC XY: 18061 AN XY: 397332

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

African (AFR) AF: 0.0491 AC: 904 AN: 18406

American (AMR) AF: 0.0462 AC: 1138 AN: 24648

Ashkenazi Jewish (ASJ) AF: 0.0515 AC: 697 AN: 13532

East Asian (EAS) AF: 0.0383 AC: 825 AN: 21538

South Asian (SAS) AF: 0.0493 AC: 2305 AN: 46726

European-Finnish (FIN) AF: 0.0234 AC: 697 AN: 29812

Middle Eastern (MID) AF: 0.0246 AC: 90 AN: 3652

European-Non Finnish (NFE) AF: 0.0473 AC: 28884 AN: 610436

Other (OTH) AF: 0.0459 AC: 1484 AN: 32330

⚠️ 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 AF: 0.00161 AC: 238 AN: 147850 Hom.: 1 Cov.: 32 AF XY: 0.00170 AC XY: 122 AN XY: 71954

African (AFR) AF: 0.00460 AC: 186 AN: 40468

American (AMR) AF: 0.000473 AC: 7 AN: 14784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.00176 AC: 9 AN: 5100

South Asian (SAS) AF: 0.000642 AC: 3 AN: 4676

European-Finnish (FIN) AF: 0.00124 AC: 12 AN: 9648

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

European-Non Finnish (NFE) AF: 0.000225 AC: 15 AN: 66550

Other (OTH) AF: 0.00295 AC: 6 AN: 2032

Alfa AF: 0.0575 Hom.: 1

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	CIC-rearranged sarcoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.47
Mutation Taster		=181/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: COSV71702310;