chr7-144259336-A-G

Position:

• chr7-144259336-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001005328.2(OR2A7):​c.293T>C​(p.Met98Thr) 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 17)
  • Exomes 𝑓: 0.00083 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2A7 NM_001005328.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.830

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.033616513).
• BP6: Variant 7-144259336-A-G is Benign according to our data. Variant chr7-144259336-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3205021.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2A7	NM_001005328.2	c.293T>C	p.Met98Thr	missense_variant	2/2	ENST00000641841.1	NP_001005328.1
ARHGEF34P	NR_033942.1	n.3864T>C		non_coding_transcript_exon_variant	13/13
ARHGEF35-AS1	NR_126022.1	n.494-21136A>G		intron_variant, non_coding_transcript_variant
OR2A1-AS1	NR_126023.1	n.608-19593T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2A7	ENST00000641841.1	c.293T>C	p.Met98Thr	missense_variant	2/2		NM_001005328.2	ENSP00000493320	P1
ARHGEF35-AS1	ENST00000460955.5	n.494-21136A>G		intron_variant, non_coding_transcript_variant		4
OR2A7	ENST00000493325.1	c.293T>C	p.Met98Thr	missense_variant	1/1			ENSP00000420502	P1

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 63 AN: 127752 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.000153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000405

Gnomad ASJ AF: 0.000960

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000815

Gnomad OTH AF: 0.000597

GnomAD3 exomes AF: 0.000507 AC: 64 AN: 126284 Hom.: 0 AF XY: 0.000416 AC XY: 28 AN XY: 67332

Gnomad AFR exome AF: 0.000139

Gnomad AMR exome AF: 0.000418

Gnomad ASJ exome AF: 0.00126

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000863

Gnomad OTH exome AF: 0.000557

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000834 AC: 743 AN: 890632 Hom.: 0 Cov.: 13 AF XY: 0.000782 AC XY: 355 AN XY: 454168

Gnomad4 AFR exome AF: 0.0000986

Gnomad4 AMR exome AF: 0.000306

Gnomad4 ASJ exome AF: 0.00114

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000505

Gnomad4 NFE exome AF: 0.00106

Gnomad4 OTH exome AF: 0.000780

GnomAD4 genome AF: 0.000493 AC: 63 AN: 127856 Hom.: 0 Cov.: 17 AF XY: 0.000393 AC XY: 24 AN XY: 61072

Gnomad4 AFR AF: 0.000152

Gnomad4 AMR AF: 0.000405

Gnomad4 ASJ AF: 0.000960

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000816

Gnomad4 OTH AF: 0.000590

Alfa AF: 0.000625 Hom.: 0

ExAC AF: 0.000117 AC: 12

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2022

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	0.091
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.095
DANN	Benign	0.28
DEOGEN2	Benign	0.0012	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0030	N
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.034	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.7	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.15	.;N
REVEL	Benign	0.025
Sift	Benign	1.0	.;T
Sift4G	Benign	0.51	.;T
Polyphen		0.0	B;B
Vest4		0.11
MVP		0.030
ClinPred		0.0044	T
GERP RS		2.1
Varity_R		0.023
gMVP		0.094

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: rs759596816; hg19: chr7-143956429; COSMIC: COSV101512222; COSMIC: COSV101512222;