19-9251062-C-A

Variant names:

• chr19-9251062-C-A
• rs541387751
• NM_001079935.2:c.19C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001079935.2(OR7E24):​c.19C>A​(p.Leu7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: OR7E24 NM_001079935.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -7.55
• Publications: 1 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06496906).

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.19C>A	p.Leu7Ile	missense	Exon 1 of 1	NP_001073404.1	Q6IFN5
	OR7E24	NM_001386108.1		c.30-23C>A		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.19C>A	p.Leu7Ile	missense	Exon 1 of 1	ENSP00000387523.1	Q6IFN5
	OR7E24	ENST00000641946.1		c.30-23C>A		intron	N/A	ENSP00000494223.1	A0A2R8Y4Q1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000464 AC: 1 AN: 215612 AF XY: 0.00000856

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000626

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1437784 Hom.: 0 Cov.: 28 AF XY: 0.00000140 AC XY: 1 AN XY: 713864

⚠️ 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: 32608

American (AMR) AF: 0.00 AC: 0 AN: 39964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25222

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39180

South Asian (SAS) AF: 0.00 AC: 0 AN: 83450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099800

Other (OTH) AF: 0.00 AC: 0 AN: 59412

⚠️ 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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.037
DANN	Benign	0.35
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N
PhyloP100		-7.6
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.0050
Sift	Benign	0.39	T
Sift4G	Benign	0.43	T
Polyphen		0.21	B
Vest4		0.091
MutPred		0.35		Gain of catalytic residue at L12 (P = 0.0491)
MVP		0.085
MPC		0.015
ClinPred		0.051	T
GERP RS		-1.4
PromoterAI		-0.0055	Neutral
Varity_R		0.051
Mutation Taster		=100/0	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: rs541387751; hg19: chr19-9361738;