19-14799455-T-A

Variant names:

• chr19-14799455-T-A
• rs202114966
• NM_001370485.4:c.682A>T

Variant summary

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

The NM_001370485.4(OR7C1):​c.682A>T​(p.Ile228Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,613,968 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: OR7C1 NM_001370485.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.468

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]

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 rank	MANE	Protein	UniProt
OR7C1	NM_001370485.4	c.682A>T	p.Ile228Phe	missense_variant	Exon 5 of 5	ENST00000641666.2	NP_001357414.2
OR7C1	NM_198944.1	c.682A>T	p.Ile228Phe	missense_variant	Exon 1 of 1		NP_945182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR7C1	ENST00000641666.2	c.682A>T	p.Ile228Phe	missense_variant	Exon 5 of 5		NM_001370485.4	ENSP00000493429.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.0000836 AC: 21 AN: 251204 Hom.: 0 AF XY: 0.0000663 AC XY: 9 AN XY: 135782

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000134 AC: 196 AN: 1461884 Hom.: 1 Cov.: 32 AF XY: 0.000127 AC XY: 92 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000842

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000153

Gnomad4 OTH exome AF: 0.0000662

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152084 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74276

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.000179 Hom.: 0

Bravo AF: 0.000113

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.682A>T (p.I228F) alteration is located in exon 1 (coding exon 1) of the OR7C1 gene. This alteration results from a A to T substitution at nucleotide position 682, causing the isoleucine (I) at amino acid position 228 to be replaced by a phenylalanine (F). 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	Benign	0.095
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.0073	T;T;T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.76	.;.;.;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.092	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.9	M;M;M;M
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.5	.;.;.;D
REVEL	Benign	0.060
Sift	Uncertain	0.0010	.;.;.;D
Sift4G	Uncertain	0.0060	.;.;.;D
Polyphen		0.99	D;D;D;D
Vest4		0.32
MVP		0.15
MPC		0.95
ClinPred		0.30	T
GERP RS		1.5
Varity_R		0.40
gMVP		0.070

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs202114966; hg19: chr19-14910267;