11-56105676-T-A

Variant names:

• chr11-56105676-T-A
• rs141783244
• NM_001386064.1:c.634T>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001386064.1(OR8H2):​c.634T>A​(p.Phe212Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,008 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: OR8H2 NM_001386064.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.57

Genes affected

OR8H2 (HGNC:15308): (olfactory receptor family 8 subfamily H member 2) 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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04230079).
• BP6: Variant 11-56105676-T-A is Benign according to our data. Variant chr11-56105676-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3303433.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR8H2	NM_001386064.1	c.634T>A	p.Phe212Ile	missense_variant	Exon 2 of 2	ENST00000313503.2	NP_001372993.1
OR8H2	NM_001005200.2	c.634T>A	p.Phe212Ile	missense_variant	Exon 2 of 2		NP_001005200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR8H2	ENST00000313503.2	c.634T>A	p.Phe212Ile	missense_variant	Exon 2 of 2	6	NM_001386064.1	ENSP00000323982.1
OR8H2	ENST00000641311.1	c.634T>A	p.Phe212Ile	missense_variant	Exon 2 of 2			ENSP00000493031.1
OR8H2	ENST00000618136.1	c.631T>A	p.Phe211Ile	missense_variant	Exon 1 of 1	6		ENSP00000482661.1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000398 AC: 10 AN: 251388 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135860

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000246 AC: 36 AN: 1461776 Hom.: 0 Cov.: 43 AF XY: 0.0000261 AC XY: 19 AN XY: 727198

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152232 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74378

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000143 Hom.: 0

Bravo AF: 0.0000945

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000576 AC: 7

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.065
DANN	Benign	0.71
DEOGEN2	Benign	0.0025	T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.0082	.;T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.042	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.98	N;N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.8	N;.;.
REVEL	Benign	0.013
Sift	Benign	0.48	T;.;.
Sift4G	Benign	0.24	T;.;T
Polyphen		0.0	B;B;.
Vest4		0.089
MVP		0.055
MPC		0.16
ClinPred		0.013	T
GERP RS		-4.5
Varity_R		0.036
gMVP		0.053

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: rs141783244; hg19: chr11-55873152; COSMIC: COSV57944988;