19-9214668-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001005191.3(OR7D4):c.170C>G(p.Thr57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,614,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: OR7D4 NM_001005191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.666

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022336334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR7D4	NM_001005191.3	c.170C>G	p.Thr57Ser	missense_variant	2/2	ENST00000641669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR7D4	ENST00000641669.1	c.170C>G	p.Thr57Ser	missense_variant	2/2		NM_001005191.3	P1
OR7D4	ENST00000308682.3	c.170C>G	p.Thr57Ser	missense_variant	1/1			P1
OR7D4	ENST00000641244.1	c.170C>G	p.Thr57Ser	missense_variant	2/2			P1

Frequencies

GnomAD3 genomes AF: 0.000453 AC: 69 AN: 152190 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000275 AC: 69 AN: 251340 Hom.: 0 AF XY: 0.000243 AC XY: 33 AN XY: 135852

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000171 AC: 250 AN: 1461864 Hom.: 0 Cov.: 33 AF XY: 0.000168 AC XY: 122 AN XY: 727234

Gnomad4 AFR exome AF: 0.000896

Gnomad4 AMR exome AF: 0.000380

Gnomad4 ASJ exome AF: 0.00111

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.000107

Gnomad4 OTH exome AF: 0.000348

GnomAD4 genome AF: 0.000453 AC: 69 AN: 152308 Hom.: 0 Cov.: 31 AF XY: 0.000349 AC XY: 26 AN XY: 74474

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000201 Hom.: 0

Bravo AF: 0.000484

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000272 AC: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.170C>G (p.T57S) alteration is located in exon 1 (coding exon 1) of the OR7D4 gene. This alteration results from a C to G substitution at nucleotide position 170, causing the threonine (T) at amino acid position 57 to be replaced by a serine (S). 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	0.10
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	18
Dann	Benign	0.91
DEOGEN2	Benign	0.012	T;T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.71	D
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.022	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;L;L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.20	T
Polyphen		0.038	B;B;B
Vest4		0.15
MutPred		0.64		Gain of disorder (P = 0.0218);Gain of disorder (P = 0.0218);Gain of disorder (P = 0.0218);
MVP		0.38
MPC		0.043
ClinPred		0.0094	T
GERP RS		-1.1
Varity_R		0.18
gMVP		0.055

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: rs149523827; hg19: chr19-9325344;