chr7-144259372-T-A

Position:

• chr7-144259372-T-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005328.2(OR2A7):​c.257A>T​(p.His86Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 19)
  • Exomes 𝑓: 0.00070 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2A7 NM_001005328.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.27

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:):

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03725314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2A7	NM_001005328.2	c.257A>T	p.His86Leu	missense_variant	2/2	ENST00000641841.1
ARHGEF34P	NR_033942.1	n.3828A>T		non_coding_transcript_exon_variant	13/13
ARHGEF35-AS1	NR_126022.1	n.494-21100T>A		intron_variant, non_coding_transcript_variant
OR2A1-AS1	NR_126023.1	n.608-19629A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2A7	ENST00000641841.1	c.257A>T	p.His86Leu	missense_variant	2/2		NM_001005328.2	P1
ARHGEF35-AS1	ENST00000460955.5	n.494-21100T>A		intron_variant, non_coding_transcript_variant		4
OR2A7	ENST00000493325.1	c.257A>T	p.His86Leu	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 196 AN: 125984 Hom.: 0 Cov.: 19 FAILED QC

Gnomad AFR AF: 0.00505

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00163

Gnomad EAS AF: 0.000207

Gnomad SAS AF: 0.000805

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00373

Gnomad NFE AF: 0.000411

Gnomad OTH AF: 0.00123

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000703 AC: 731 AN: 1040194 Hom.: 0 Cov.: 16 AF XY: 0.000677 AC XY: 357 AN XY: 527372

Gnomad4 AFR exome AF: 0.0101

Gnomad4 AMR exome AF: 0.000780

Gnomad4 ASJ exome AF: 0.00285

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000248

Gnomad4 FIN exome AF: 0.0000216

Gnomad4 NFE exome AF: 0.000454

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00155 AC: 196 AN: 126084 Hom.: 0 Cov.: 19 AF XY: 0.00137 AC XY: 83 AN XY: 60642

Gnomad4 AFR AF: 0.00503

Gnomad4 AMR AF: 0.000720

Gnomad4 ASJ AF: 0.00163

Gnomad4 EAS AF: 0.000208

Gnomad4 SAS AF: 0.000806

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000411

Gnomad4 OTH AF: 0.00121

Alfa AF: 0.00294 Hom.: 0

ExAC AF: 0.0000176 AC: 2

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

Mar 07, 2023

The c.257A>T (p.H86L) alteration is located in exon 1 (coding exon 1) of the OR2A7 gene. This alteration results from a A to T substitution at nucleotide position 257, causing the histidine (H) at amino acid position 86 to be replaced by a leucine (L). 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	0.083
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.1
DANN	Benign	0.80
DEOGEN2	Benign	0.0056	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.010	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.47	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.7	.;N
REVEL	Benign	0.029
Sift	Benign	0.23	.;T
Sift4G	Benign	0.24	.;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.28		Loss of methylation at K89 (P = 0.0617);Loss of methylation at K89 (P = 0.0617);
MVP		0.16
ClinPred		0.0011	T
GERP RS		-2.4
Varity_R		0.085
gMVP		0.15

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

Publications

LitVar

Other links and lift over

dbSNP: rs755621211; hg19: chr7-143956465; COSMIC: COSV71828279; COSMIC: COSV71828279;