7-144259175-C-T

Variant names:

• chr7-144259175-C-T
• rs768275435
• NM_001005328.2:c.454G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005328.2(OR2A7):​c.454G>A​(p.Val152Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0000075 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2A7 NM_001005328.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.51
• Publications: 0 publications found

Genes affected

OR2A7 (HGNC:8234): (olfactory receptor family 2 subfamily A member 7) 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]

ARHGEF34P (HGNC:38086): (Rho guanine nucleotide exchange factor 34, pseudogene)

ARHGEF35-AS1 (HGNC:41292): (ARHGEF35 antisense RNA 1)

OR2A1-AS1 (HGNC:49168): (OR2A1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09931484).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005328.2. 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
	OR2A7	NM_001005328.2	MANE Select	c.454G>A	p.Val152Ile	missense	Exon 2 of 2	NP_001005328.1	Q96R45
	ARHGEF34P	NR_033942.1		n.4025G>A		non_coding_transcript_exon	Exon 13 of 13
	ARHGEF35-AS1	NR_126022.1		n.494-21297C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2A7	ENST00000641841.1	MANE Select	c.454G>A	p.Val152Ile	missense	Exon 2 of 2	ENSP00000493320.1	Q96R45
	OR2A7	ENST00000493325.1	TSL:6	c.454G>A	p.Val152Ile	missense	Exon 1 of 1	ENSP00000420502.1	Q96R45
	ARHGEF35-AS1	ENST00000460955.5	TSL:4	n.494-21297C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000152 AC: 2 AN: 131422 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000569

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000749 AC: 8 AN: 1068032 Hom.: 0 Cov.: 16 AF XY: 0.00000557 AC XY: 3 AN XY: 538818

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25330

American (AMR) AF: 0.00 AC: 0 AN: 34824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22148

East Asian (EAS) AF: 0.00 AC: 0 AN: 36842

South Asian (SAS) AF: 0.00 AC: 0 AN: 72124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4178

European-Non Finnish (NFE) AF: 0.0000103 AC: 8 AN: 779618

Other (OTH) AF: 0.00 AC: 0 AN: 46882

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000152 AC: 2 AN: 131422 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 62678

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000569 AC: 2 AN: 35132

American (AMR) AF: 0.00 AC: 0 AN: 12706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3164

East Asian (EAS) AF: 0.00 AC: 0 AN: 5010

South Asian (SAS) AF: 0.00 AC: 0 AN: 3758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60890

Other (OTH) AF: 0.00 AC: 0 AN: 1706

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.22
DANN	Benign	0.89
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.038	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.17	N
PhyloP100		-1.5
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.014
Sift	Benign	0.26	T
Sift4G	Benign	0.27	T
Polyphen		0.013	B
Vest4		0.033
MutPred		0.42		Loss of catalytic residue at V152 (P = 0.1315)
MVP		0.067
ClinPred		0.073	T
GERP RS		0.93
Varity_R		0.022
gMVP		0.037
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs768275435; hg19: chr7-143956268;