7-144258886-C-T

Variant names:

• chr7-144258886-C-T
• rs757342704
• NM_001005328.2:c.743G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005328.2(OR2A7):​c.743G>A​(p.Gly248Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G248V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2A7 NM_001005328.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666
• Publications: 1 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]

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

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2606038).

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.743G>A	p.Gly248Glu	missense	Exon 2 of 2	NP_001005328.1	Q96R45
	ARHGEF35-AS1	NR_126022.1		n.494-21586C>T		intron	N/A
	OR2A1-AS1	NR_126023.1		n.608-19143G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2A7	ENST00000641841.1	MANE Select	c.743G>A	p.Gly248Glu	missense	Exon 2 of 2	ENSP00000493320.1	Q96R45
	OR2A7	ENST00000493325.1	TSL:6	c.743G>A	p.Gly248Glu	missense	Exon 1 of 1	ENSP00000420502.1	Q96R45
	ARHGEF35-AS1	ENST00000460955.5	TSL:4	n.494-21586C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251354 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461534 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727076

⚠️ 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: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111904

Other (OTH) AF: 0.00 AC: 0 AN: 60382

⚠️ 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 Cov.: 22

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.067	N
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.67
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.14
Sift	Benign	0.038	D
Sift4G	Benign	0.34	T
Polyphen		0.86	P
Vest4		0.44
MutPred		0.61		Loss of catalytic residue at L249 (P = 0.1137)
MVP		0.42
ClinPred		0.77	D
GERP RS		2.3
Varity_R		0.45
gMVP		0.13
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs757342704; hg19: chr7-143955979;