19-14827508-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017506.2(OR7A5):c.734T>G(p.Leu245Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000133 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: OR7A5 NM_017506.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.16

Genes affected

OR7A5 (HGNC:8368): (olfactory receptor family 7 subfamily A member 5) 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]

OR7C1 (HGNC:8373): (olfactory receptor family 7 subfamily C member 1) 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR7A5	NM_017506.2	c.734T>G	p.Leu245Arg	missense_variant	2/2	ENST00000322301.5
OR7C1	NM_001370485.4	c.-623+7566T>G		intron_variant		ENST00000641666.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR7A5	ENST00000322301.5	c.734T>G	p.Leu245Arg	missense_variant	2/2		NM_017506.2	P1
OR7C1	ENST00000641666.2	c.-623+7566T>G		intron_variant			NM_001370485.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000151 AC: 38 AN: 251404 Hom.: 0 AF XY: 0.000162 AC XY: 22 AN XY: 135878

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000138 AC: 202 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.000146 AC XY: 106 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00172

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000111

Gnomad4 OTH exome AF: 0.000199

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74334

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000247 Hom.: 0

Bravo AF: 0.000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000123 AC: 15

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.734T>G (p.L245R) alteration is located in exon 1 (coding exon 1) of the OR7A5 gene. This alteration results from a T to G substitution at nucleotide position 734, causing the leucine (L) at amino acid position 245 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.11
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.053	T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.0024	T
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Uncertain	0.092	D
MutationAssessor	Pathogenic	4.7	H;H
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.19	T
PROVEAN	Pathogenic	-5.6	D;.
REVEL	Uncertain	0.39
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.58
MVP		0.80
MPC		0.41
ClinPred		0.67	D
GERP RS		3.1
Varity_R		0.80
gMVP		0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs201863024; hg19: chr19-14938320;