rs8109935

Variant names:

• chr19-9214187-G-A
• rs8109935
• NM_001005191.3:c.651C>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.651C>T​(p.Ser217Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 1,613,186 control chromosomes in the GnomAD database, including 10,447 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 0.15 (2773 hom., cov: 31)
  • Exomes 𝑓: 0.089 (7674 hom.)
• Consequence: OR7D4 NM_001005191.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246
• Publications: 12 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 (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR7D4	NM_001005191.3	c.651C>T	p.Ser217Ser	synonymous_variant	Exon 2 of 2	ENST00000641669.1	NP_001005191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR7D4	ENST00000641669.1	c.651C>T	p.Ser217Ser	synonymous_variant	Exon 2 of 2		NM_001005191.3	ENSP00000493383.1
OR7D4	ENST00000308682.3	c.651C>T	p.Ser217Ser	synonymous_variant	Exon 1 of 1	6		ENSP00000310488.2
OR7D4	ENST00000641244.1	c.651C>T	p.Ser217Ser	synonymous_variant	Exon 2 of 2			ENSP00000493404.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22728 AN: 151974 Hom.: 2766 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.0504

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0269

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.0746

Gnomad OTH AF: 0.145

GnomAD2 exomes AF: 0.109 AC: 27439 AN: 251330 AF XY: 0.110

Gnomad AFR exome AF: 0.332

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.0543

Gnomad FIN exome AF: 0.0285

Gnomad NFE exome AF: 0.0763

Gnomad OTH exome AF: 0.0985

GnomAD4 exome AF: 0.0892 AC: 130318 AN: 1461094 Hom.: 7674 Cov.: 33 AF XY: 0.0925 AC XY: 67206 AN XY: 726884

African (AFR) AF: 0.335 AC: 11155 AN: 33254

American (AMR) AF: 0.120 AC: 5341 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2836 AN: 26136

East Asian (EAS) AF: 0.0423 AC: 1677 AN: 39660

South Asian (SAS) AF: 0.202 AC: 17410 AN: 86174

European-Finnish (FIN) AF: 0.0298 AC: 1592 AN: 53418

Middle Eastern (MID) AF: 0.167 AC: 965 AN: 5766

European-Non Finnish (NFE) AF: 0.0746 AC: 82894 AN: 1111650

Other (OTH) AF: 0.107 AC: 6448 AN: 60360

GnomAD4 genome AF: 0.150 AC: 22763 AN: 152092 Hom.: 2773 Cov.: 31 AF XY: 0.148 AC XY: 10994 AN XY: 74354

African (AFR) AF: 0.324 AC: 13428 AN: 41438

American (AMR) AF: 0.128 AC: 1955 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3468

East Asian (EAS) AF: 0.0505 AC: 261 AN: 5166

South Asian (SAS) AF: 0.205 AC: 986 AN: 4808

European-Finnish (FIN) AF: 0.0269 AC: 285 AN: 10614

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0746 AC: 5071 AN: 68008

Other (OTH) AF: 0.144 AC: 304 AN: 2112

Alfa AF: 0.114 Hom.: 907

Bravo AF: 0.164

Asia WGS AF: 0.129 AC: 451 AN: 3478

EpiCase AF: 0.0864

EpiControl AF: 0.0869

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.0
DANN	Benign	0.33
PhyloP100		-0.25
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs8109935; hg19: chr19-9324863; COSMIC: COSV58071723; COSMIC: COSV58071723;