rs61729907

Variant names:

• chr19-9214576-G-A
• rs61729907
• NM_001005191.3:c.262C>T

Variant summary

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

The NM_001005191.3(OR7D4):​c.262C>T​(p.Arg88Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,613,596 control chromosomes in the GnomAD database, including 24,793 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.15 (2009 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22784 hom.)
• Consequence: OR7D4 NM_001005191.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• Publications: 39 publications found

Genes affected

OR7D4 (HGNC:8380): (olfactory receptor family 7 subfamily D member 4) 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]

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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007482052).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005191.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR7D4	NM_001005191.3	MANE Select	c.262C>T	p.Arg88Trp	missense	Exon 2 of 2	NP_001005191.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR7D4	ENST00000641669.1	MANE Select	c.262C>T	p.Arg88Trp	missense	Exon 2 of 2	ENSP00000493383.1
	OR7D4	ENST00000308682.3	TSL:6	c.262C>T	p.Arg88Trp	missense	Exon 1 of 1	ENSP00000310488.2
	OR7D4	ENST00000641244.1		c.262C>T	p.Arg88Trp	missense	Exon 2 of 2	ENSP00000493404.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 23011 AN: 152020 Hom.: 2009 Cov.: 32

Gnomad AFR AF: 0.0760

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.171

GnomAD2 exomes AF: 0.170 AC: 42862 AN: 251422 AF XY: 0.175

Gnomad AFR exome AF: 0.0741

Gnomad AMR exome AF: 0.0906

Gnomad ASJ exome AF: 0.208

Gnomad EAS exome AF: 0.226

Gnomad FIN exome AF: 0.250

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.174 AC: 253564 AN: 1461458 Hom.: 22784 Cov.: 34 AF XY: 0.174 AC XY: 126750 AN XY: 727056

African (AFR) AF: 0.0735 AC: 2459 AN: 33468

American (AMR) AF: 0.0936 AC: 4186 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5333 AN: 26128

East Asian (EAS) AF: 0.232 AC: 9193 AN: 39694

South Asian (SAS) AF: 0.188 AC: 16232 AN: 86254

European-Finnish (FIN) AF: 0.244 AC: 13026 AN: 53420

Middle Eastern (MID) AF: 0.227 AC: 1309 AN: 5764

European-Non Finnish (NFE) AF: 0.172 AC: 190971 AN: 1111626

Other (OTH) AF: 0.180 AC: 10855 AN: 60380

GnomAD4 genome AF: 0.151 AC: 23011 AN: 152138 Hom.: 2009 Cov.: 32 AF XY: 0.156 AC XY: 11579 AN XY: 74366

African (AFR) AF: 0.0758 AC: 3147 AN: 41530

American (AMR) AF: 0.126 AC: 1919 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 688 AN: 3468

East Asian (EAS) AF: 0.226 AC: 1167 AN: 5154

South Asian (SAS) AF: 0.182 AC: 876 AN: 4816

European-Finnish (FIN) AF: 0.253 AC: 2683 AN: 10592

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11945 AN: 67980

Other (OTH) AF: 0.174 AC: 368 AN: 2114

Alfa AF: 0.163 Hom.: 3433

Bravo AF: 0.137

TwinsUK AF: 0.161 AC: 598

ALSPAC AF: 0.170 AC: 655

ESP6500AA AF: 0.0794 AC: 350

ESP6500EA AF: 0.183 AC: 1572

ExAC AF: 0.169 AC: 20510

Asia WGS AF: 0.193 AC: 670 AN: 3478

EpiCase AF: 0.181

EpiControl AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0075	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.74	N
PhyloP100		-2.7
PrimateAI	Benign	0.17	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.050
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.84	P
Vest4		0.037
MPC		0.071
ClinPred		0.033	T
GERP RS		0.41
PromoterAI		-0.0031	Neutral
Varity_R		0.12
gMVP		0.071
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61729907; hg19: chr19-9325252; COSMIC: COSV58071249; COSMIC: COSV58071249;