Genetic Variant NM_001004486.1:c.549C>G (chrX-131544622-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_001004486.1(OR13H1):c.549C>G(p.Leu183Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,207,438 control chromosomes in the GnomAD database, including 46,625 homozygotes. There are 130,590 hemizygotes in GnomAD. 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 0.24 ( 3072 hom., 7884 hem., cov: 22)

Exomes 𝑓: 0.34 ( 43553 hom. 122706 hem. )

Consequence

OR13H1
NM_001004486.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.31

Publications

12 publications found

Variant links:

Genes affected

OR13H1 (HGNC:14755): (olfactory receptor family 13 subfamily H 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. [provided by RefSeq, Jul 2008]

OR13H1 links:

IGSF1 (HGNC:5948): (immunoglobulin superfamily member 1) This gene encodes a member of the immunoglobulin-like domain-containing superfamily. Proteins in this superfamily contain varying numbers of immunoglobulin-like domains and are thought to participate in the regulation of interactions between cells. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2010]

IGSF1 Gene-Disease associations (from GenCC):

X-linked central congenital hypothyroidism with late-onset testicular enlargement
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

IGSF1 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=-0.82).

BP7

Synonymous conserved (PhyloP=-2.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR13H1	NM_001004486.1 link	c.549C>G	p.Leu183Leu	synonymous_variant	Exon 1 of 1	ENST00000338616.6	NP_001004486.1	Q8NG92A0A126GW70

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR13H1	ENST00000338616.6 link	c.549C>G	p.Leu183Leu	synonymous_variant	Exon 1 of 1	6	NM_001004486.1	ENSP00000340748.3		Q8NG92
IGSF1	ENST00000370904.6 link	c.-913+34046G>C		intron_variant	Intron 1 of 26	2		ENSP00000359941.1		Q8N6C5-2

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

26935

AN:

110974

Hom.:

3074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0522

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.0428

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.254

GnomAD2 exomes

AF:

0.277

AC:

50511

AN:

182641

AF XY:

0.298

show subpopulations

Gnomad AFR exome

AF:

0.0456

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.354

Gnomad EAS exome

AF:

0.0440

Gnomad FIN exome

AF:

0.338

Gnomad NFE exome

AF:

0.353

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.336

AC:

368274

AN:

1096415

Hom.:

43553

Cov.:

AF XY:

0.339

AC XY:

122706

AN XY:

362007

show subpopulations

African (AFR)

AF:

0.0433

AC:

1143

AN:

26380

American (AMR)

AF:

0.170

AC:

5988

AN:

35196

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

6867

AN:

19362

East Asian (EAS)

AF:

0.0527

AC:

1592

AN:

30200

South Asian (SAS)

AF:

0.347

AC:

18770

AN:

54067

European-Finnish (FIN)

AF:

0.334

AC:

13512

AN:

40501

Middle Eastern (MID)

AF:

0.439

AC:

1816

AN:

4134

European-Non Finnish (NFE)

AF:

0.362

AC:

304285

AN:

840535

Other (OTH)

AF:

0.311

AC:

14301

AN:

46040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

9136

18273

27409

36546

45682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10284

20568

30852

41136

51420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.243

AC:

26930

AN:

111023

Hom.:

3072

Cov.:

AF XY:

0.237

AC XY:

7884

AN XY:

33249

show subpopulations

African (AFR)

AF:

0.0521

AC:

1601

AN:

30741

American (AMR)

AF:

0.212

AC:

2196

AN:

10382

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

941

AN:

2632

East Asian (EAS)

AF:

0.0432

AC:

153

AN:

3539

South Asian (SAS)

AF:

0.331

AC:

862

AN:

2607

European-Finnish (FIN)

AF:

0.321

AC:

1888

AN:

5879

Middle Eastern (MID)

AF:

0.468

AC:

101

AN:

216

European-Non Finnish (NFE)

AF:

0.351

AC:

18526

AN:

52848

Other (OTH)

AF:

0.255

AC:

385

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

680

1360

2040

2720

3400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.300

Hom.:

2909

Bravo

AF:

0.226

EpiCase

AF:

0.375

EpiControl

AF:

0.376

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.3

(source)

DANN

Benign

0.58

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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