19-14799626-C-T

Variant names:

• chr19-14799626-C-T
• rs10415312
• NM_001370485.4:c.511G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370485.4(OR7C1):​c.511G>A​(p.Glu171Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 1,614,044 control chromosomes in the GnomAD database, including 682,648 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.94 (66785 hom., cov: 30)
  • Exomes 𝑓: 0.92 (615863 hom.)
• Consequence: OR7C1 NM_001370485.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.03
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3848052E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370485.4. 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
	OR7C1	NM_001370485.4	MANE Select	c.511G>A	p.Glu171Lys	missense	Exon 5 of 5	NP_001357414.2	A0A126GWU6
	OR7C1	NM_198944.1		c.511G>A	p.Glu171Lys	missense	Exon 1 of 1	NP_945182.1	O76099

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR7C1	ENST00000641666.2	MANE Select	c.511G>A	p.Glu171Lys	missense	Exon 5 of 5	ENSP00000493429.1	O76099
	OR7C1	ENST00000248073.2	TSL:6	c.511G>A	p.Glu171Lys	missense	Exon 1 of 1	ENSP00000248073.2	O76099
	OR7C1	ENST00000642000.1		c.511G>A	p.Glu171Lys	missense	Exon 3 of 3	ENSP00000493248.1	O76099

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142308 AN: 152036 Hom.: 66725 Cov.: 30

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.940

GnomAD2 exomes AF: 0.935 AC: 235213 AN: 251444 AF XY: 0.934

Gnomad AFR exome AF: 0.984

Gnomad AMR exome AF: 0.957

Gnomad ASJ exome AF: 0.918

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.909

Gnomad NFE exome AF: 0.906

Gnomad OTH exome AF: 0.924

GnomAD4 exome AF: 0.917 AC: 1341185 AN: 1461890 Hom.: 615863 Cov.: 78 AF XY: 0.919 AC XY: 668103 AN XY: 727246

African (AFR) AF: 0.986 AC: 32996 AN: 33480

American (AMR) AF: 0.955 AC: 42721 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 23959 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39694 AN: 39700

South Asian (SAS) AF: 0.983 AC: 84783 AN: 86258

European-Finnish (FIN) AF: 0.906 AC: 48418 AN: 53420

Middle Eastern (MID) AF: 0.937 AC: 5405 AN: 5768

European-Non Finnish (NFE) AF: 0.906 AC: 1007273 AN: 1112008

Other (OTH) AF: 0.926 AC: 55936 AN: 60396

GnomAD4 genome AF: 0.936 AC: 142428 AN: 152154 Hom.: 66785 Cov.: 30 AF XY: 0.938 AC XY: 69770 AN XY: 74386

African (AFR) AF: 0.983 AC: 40787 AN: 41510

American (AMR) AF: 0.938 AC: 14325 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3206 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5187 AN: 5188

South Asian (SAS) AF: 0.984 AC: 4739 AN: 4814

European-Finnish (FIN) AF: 0.907 AC: 9604 AN: 10584

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61509 AN: 68002

Other (OTH) AF: 0.941 AC: 1983 AN: 2108

Alfa AF: 0.919 Hom.: 146876

Bravo AF: 0.939

TwinsUK AF: 0.907 AC: 3365

ALSPAC AF: 0.905 AC: 3487

ESP6500AA AF: 0.984 AC: 4337

ESP6500EA AF: 0.910 AC: 7824

ExAC AF: 0.935 AC: 113544

Asia WGS AF: 0.989 AC: 3441 AN: 3478

EpiCase AF: 0.907

EpiControl AF: 0.906

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.032
DANN	Benign	0.79
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0045	N
LIST_S2	Benign	0.047	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.61	N
PhyloP100		-7.0
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.019
Sift	Benign	0.20	T
Sift4G	Benign	0.14	T
Polyphen		0.017	B
Vest4		0.041
MPC		0.24
ClinPred		0.012	T
GERP RS		-7.3
Varity_R		0.073
gMVP		0.14
Mutation Taster		=99/1	polymorphism (auto)

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: rs10415312; hg19: chr19-14910438; COSMIC: COSV107214654;