19-14829189-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370485.4(OR7C1):c.-623+5885A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,014 control chromosomes in the GnomAD database, including 6,847 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6847 hom., cov: 32)
• Consequence: OR7C1 NM_001370485.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR7C1	NM_001370485.4	c.-623+5885A>G		intron_variant		ENST00000641666.2
OR7A5	NM_017506.2	c.-13-935A>G		intron_variant		ENST00000322301.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR7A5	ENST00000322301.5	c.-13-935A>G		intron_variant			NM_017506.2	P1
OR7C1	ENST00000641666.2	c.-623+5885A>G		intron_variant			NM_001370485.4	P1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44393 AN: 151896 Hom.: 6830 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44435 AN: 152014 Hom.: 6847 Cov.: 32 AF XY: 0.298 AC XY: 22126 AN XY: 74310

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.267

Alfa AF: 0.254 Hom.: 3078

Bravo AF: 0.289

Asia WGS AF: 0.471 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	2.3
Dann	Benign	0.41

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: rs8101893; hg19: chr19-14940001;