19-9251064-C-CT

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_001079935.2(OR7E24):c.32dup(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

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

Verdict is Likely_benign. Variant got -1 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0462 (37024/801080) while in subpopulation SAS AF= 0.0493 (2305/46726). AF 95% confidence interval is 0.0477. There are 1 homozygotes in gnomad4_exome. There are 18061 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR7E24	NM_001079935.2	c.32dup	p.Leu12ProfsTer59	frameshift_variant	1/1	ENST00000456448.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR7E24	ENST00000456448.3	c.32dup	p.Leu12ProfsTer59	frameshift_variant	1/1		NM_001079935.2	P2
OR7E24	ENST00000641946.1	c.30-10dup		intron_variant				A2

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

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

Gnomad4 AFR exome AF: 0.0491

Gnomad4 AMR exome AF: 0.0462

Gnomad4 ASJ exome AF: 0.0515

Gnomad4 EAS exome AF: 0.0383

Gnomad4 SAS exome AF: 0.0493

Gnomad4 FIN exome AF: 0.0234

Gnomad4 NFE exome AF: 0.0473

Gnomad4 OTH exome AF: 0.0459

GnomAD4 genome AF: 0.00161 AC: 238 AN: 147850 Hom.: 1 Cov.: 32 AF XY: 0.00170 AC XY: 122 AN XY: 71954

Gnomad4 AFR AF: 0.00460

Gnomad4 AMR AF: 0.000473

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00176

Gnomad4 SAS AF: 0.000642

Gnomad4 FIN AF: 0.00124

Gnomad4 NFE AF: 0.000225

Gnomad4 OTH AF: 0.00295

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

CIC-DUX Sarcoma Other:1

not provided, no classification provided

literature only

Children's Cancer Therapy Development Institute

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs201985790; hg19: chr19-9361740;