19-9251064-CTTT-CTT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001079935.2(OR7E24):​c.32delT​(p.Phe11SerfsTer89) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,074,790 control chromosomes in the GnomAD database, including 21 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 32)
  • Exomes 𝑓: 0.017 (19 hom.)
• Consequence: OR7E24 NM_001079935.2 frameshift
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.32delT	p.Phe11SerfsTer89	frameshift	Exon 1 of 1	NP_001073404.1	Q6IFN5
	OR7E24	NM_001386108.1		c.30-10delT		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.32delT	p.Phe11SerfsTer89	frameshift	Exon 1 of 1	ENSP00000387523.1	Q6IFN5
	OR7E24	ENST00000641946.1		c.30-10delT		intron	N/A	ENSP00000494223.1	A0A2R8Y4Q1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 157 AN: 147776 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000867

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000271

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.00149

Gnomad FIN AF: 0.000104

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.000270

Gnomad OTH AF: 0.000991

GnomAD2 exomes AF: 0.120 AC: 8155 AN: 67898 AF XY: 0.130

Gnomad AFR exome AF: 0.0902

Gnomad AMR exome AF: 0.120

Gnomad ASJ exome AF: 0.131

Gnomad EAS exome AF: 0.135

Gnomad FIN exome AF: 0.0785

Gnomad NFE exome AF: 0.128

Gnomad OTH exome AF: 0.105

GnomAD4 exome AF: 0.0171 AC: 15823 AN: 926936 Hom.: 19 Cov.: 30 AF XY: 0.0182 AC XY: 8380 AN XY: 459658

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

African (AFR) AF: 0.0186 AC: 391 AN: 21074

American (AMR) AF: 0.0394 AC: 1052 AN: 26704

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 369 AN: 15640

East Asian (EAS) AF: 0.0621 AC: 1546 AN: 24906

South Asian (SAS) AF: 0.0259 AC: 1374 AN: 53088

European-Finnish (FIN) AF: 0.0200 AC: 650 AN: 32494

Middle Eastern (MID) AF: 0.0113 AC: 45 AN: 3978

European-Non Finnish (NFE) AF: 0.0137 AC: 9758 AN: 711350

Other (OTH) AF: 0.0169 AC: 638 AN: 37702

⚠️ 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: 0.00106 AC: 157 AN: 147854 Hom.: 2 Cov.: 32 AF XY: 0.000973 AC XY: 70 AN XY: 71948

African (AFR) AF: 0.000865 AC: 35 AN: 40468

American (AMR) AF: 0.000270 AC: 4 AN: 14788

Ashkenazi Jewish (ASJ) AF: 0.000293 AC: 1 AN: 3412

East Asian (EAS) AF: 0.0173 AC: 88 AN: 5098

South Asian (SAS) AF: 0.00150 AC: 7 AN: 4672

European-Finnish (FIN) AF: 0.000104 AC: 1 AN: 9654

Middle Eastern (MID) AF: 0.00352 AC: 1 AN: 284

European-Non Finnish (NFE) AF: 0.000270 AC: 18 AN: 66546

Other (OTH) AF: 0.000982 AC: 2 AN: 2036

Alfa AF: 0.0360 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.47
Mutation Taster		=187/13	polymorphism

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: COSV71702119;