Genetic Variant NM_001348233.2:c.-367T>C (chr14-22644437-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001348233.2(OR6J1):c.-367T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,048 control chromosomes in the GnomAD database, including 27,431 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 27429 hom., cov: 31)

Exomes 𝑓: 0.50 ( 2 hom. )

Consequence

OR6J1
NM_001348233.2 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.413

Publications

8 publications found

Variant links:

Genes affected

OR6J1 (HGNC:14707): (olfactory receptor family 6 subfamily J member 1) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jan 2017]

OR6J1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR6J1	NM_001348233.2 link	c.-367T>C		upstream_gene_variant		ENST00000540461.2	NP_001335162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR6J1	ENST00000540461.2 link	c.-367T>C		upstream_gene_variant		6	NM_001348233.2	ENSP00000437629.1		Q8NGC5

Frequencies

GnomAD3 genomes

AF:

0.581

AC:

88234

AN:

151914

Hom.:

27393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.809

Gnomad AMI

AF:

0.622

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.498

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.529

Gnomad OTH

AF:

0.532

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.625

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.581

AC:

88309

AN:

152034

Hom.:

27429

Cov.:

AF XY:

0.573

AC XY:

42553

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.809

AC:

33556

AN:

41480

American (AMR)

AF:

0.417

AC:

6368

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

1576

AN:

3466

East Asian (EAS)

AF:

0.274

AC:

1415

AN:

5168

South Asian (SAS)

AF:

0.487

AC:

2348

AN:

4826

European-Finnish (FIN)

AF:

0.498

AC:

5263

AN:

10564

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.529

AC:

35958

AN:

67944

Other (OTH)

AF:

0.525

AC:

1107

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1727

3455

5182

6910

8637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.537

Hom.:

38712

Bravo

AF:

0.581

Asia WGS

AF:

0.363

AC:

1266

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.5

(source)

DANN

Benign

0.44

PhyloP100

-0.41

PromoterAI

-0.023

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over