Genetic Variant NM_001005486.2:c.123C>G (chr14-19975713-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001005486.2(OR4K15):c.123C>G(p.Gly41Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,612,398 control chromosomes in the GnomAD database, including 77,694 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. Synonymous variant affecting the same amino acid position (i.e. G41G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.38 ( 13975 hom., cov: 31)

Exomes 𝑓: 0.28 ( 63719 hom. )

Consequence

OR4K15
NM_001005486.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.44

Publications

8 publications found

Variant links:

Genes affected

OR4K15 (HGNC:15353): (olfactory receptor family 4 subfamily K member 15) 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]

OR4K15 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP7

Synonymous conserved (PhyloP=-4.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4K15	NM_001005486.2 link	c.123C>G	p.Gly41Gly	synonymous_variant	Exon 1 of 1	ENST00000305051.6	NP_001005486.2	Q8NH41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4K15	ENST00000305051.6 link	c.123C>G	p.Gly41Gly	synonymous_variant	Exon 1 of 1	6	NM_001005486.2	ENSP00000304077.5		Q8NH41

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57781

AN:

151474

Hom.:

13940

Cov.:

show subpopulations

Gnomad AFR

AF:

0.696

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.339

GnomAD2 exomes

AF:

0.281

AC:

70457

AN:

250728

AF XY:

0.281

show subpopulations

Gnomad AFR exome

AF:

0.703

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.228

Gnomad NFE exome

AF:

0.275

Gnomad OTH exome

AF:

0.264

GnomAD4 exome

AF:

0.284

AC:

414609

AN:

1460806

Hom.:

63719

Cov.:

AF XY:

0.284

AC XY:

206728

AN XY:

726766

show subpopulations

African (AFR)

AF:

0.714

AC:

23869

AN:

33426

American (AMR)

AF:

0.186

AC:

8304

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

5394

AN:

26110

East Asian (EAS)

AF:

0.151

AC:

5985

AN:

39692

South Asian (SAS)

AF:

0.348

AC:

29993

AN:

86236

European-Finnish (FIN)

AF:

0.227

AC:

12118

AN:

53392

Middle Eastern (MID)

AF:

0.310

AC:

1783

AN:

5758

European-Non Finnish (NFE)

AF:

0.279

AC:

309509

AN:

1111154

Other (OTH)

AF:

0.293

AC:

17654

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

15292

30583

45875

61166

76458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.382

AC:

57861

AN:

151592

Hom.:

13975

Cov.:

AF XY:

0.376

AC XY:

27880

AN XY:

74066

show subpopulations

African (AFR)

AF:

0.696

AC:

28740

AN:

41266

American (AMR)

AF:

0.253

AC:

3840

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

723

AN:

3456

East Asian (EAS)

AF:

0.148

AC:

761

AN:

5134

South Asian (SAS)

AF:

0.352

AC:

1690

AN:

4798

European-Finnish (FIN)

AF:

0.223

AC:

2352

AN:

10524

Middle Eastern (MID)

AF:

0.288

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.277

AC:

18802

AN:

67920

Other (OTH)

AF:

0.337

AC:

706

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1501

3002

4503

6004

7505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.202

Hom.:

589

Bravo

AF:

0.392

EpiCase

AF:

0.275

EpiControl

AF:

0.270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.5

(source)

DANN

Benign

0.53

PhyloP100

-4.4

PromoterAI

-0.023

Neutral

(source)

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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NM_001005486.2:c.123C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over