1-248324336-A-G

Variant names:

• chr1-248324336-A-G
• rs7555310
• NM_001004691.1:c.233T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004691.1(OR2M7):​c.233T>C​(p.Val78Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,613,894 control chromosomes in the GnomAD database, including 456,755 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (44847 hom., cov: 31)
  • Exomes 𝑓: 0.75 (411908 hom.)
• Consequence: OR2M7 NM_001004691.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 25 publications found

Genes affected

OR2M7 (HGNC:19594): (olfactory receptor family 2 subfamily M 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.5854079E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2M7	NM_001004691.1	c.233T>C	p.Val78Ala	missense_variant	Exon 1 of 1	ENST00000317965.3	NP_001004691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2M7	ENST00000317965.3	c.233T>C	p.Val78Ala	missense_variant	Exon 1 of 1	6	NM_001004691.1	ENSP00000324557.2

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116407 AN: 151974 Hom.: 44816 Cov.: 31

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.750

GnomAD2 exomes AF: 0.774 AC: 194513 AN: 251346 AF XY: 0.777

Gnomad AFR exome AF: 0.775

Gnomad AMR exome AF: 0.772

Gnomad ASJ exome AF: 0.705

Gnomad EAS exome AF: 0.864

Gnomad FIN exome AF: 0.799

Gnomad NFE exome AF: 0.739

Gnomad OTH exome AF: 0.755

GnomAD4 exome AF: 0.750 AC: 1095897 AN: 1461802 Hom.: 411908 Cov.: 97 AF XY: 0.753 AC XY: 547504 AN XY: 727202

African (AFR) AF: 0.777 AC: 26014 AN: 33476

American (AMR) AF: 0.771 AC: 34462 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.702 AC: 18344 AN: 26130

East Asian (EAS) AF: 0.845 AC: 33546 AN: 39698

South Asian (SAS) AF: 0.860 AC: 74129 AN: 86246

European-Finnish (FIN) AF: 0.801 AC: 42759 AN: 53406

Middle Eastern (MID) AF: 0.744 AC: 4287 AN: 5764

European-Non Finnish (NFE) AF: 0.734 AC: 816565 AN: 1111970

Other (OTH) AF: 0.758 AC: 45791 AN: 60392

GnomAD4 genome AF: 0.766 AC: 116493 AN: 152092 Hom.: 44847 Cov.: 31 AF XY: 0.771 AC XY: 57344 AN XY: 74344

African (AFR) AF: 0.780 AC: 32329 AN: 41462

American (AMR) AF: 0.777 AC: 11860 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2430 AN: 3470

East Asian (EAS) AF: 0.859 AC: 4448 AN: 5178

South Asian (SAS) AF: 0.874 AC: 4213 AN: 4820

European-Finnish (FIN) AF: 0.802 AC: 8496 AN: 10598

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50141 AN: 67974

Other (OTH) AF: 0.749 AC: 1585 AN: 2116

Alfa AF: 0.742 Hom.: 78116

Bravo AF: 0.762

TwinsUK AF: 0.727 AC: 2694

ALSPAC AF: 0.741 AC: 2854

ESP6500AA AF: 0.776 AC: 3420

ESP6500EA AF: 0.747 AC: 6420

ExAC AF: 0.776 AC: 94168

Asia WGS AF: 0.855 AC: 2969 AN: 3478

EpiCase AF: 0.731

EpiControl AF: 0.738

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0000026	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.40
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.038
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.024	D
Polyphen		0.97	D
Vest4		0.015
MPC		0.12
ClinPred		0.034	T
GERP RS		-0.011
PromoterAI		0.0015	Neutral
Varity_R		0.34
gMVP		0.24
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7555310; hg19: chr1-248487638; COSMIC: COSV107375158;