NM_006398.4:c.198T>C

Variant names:

Variant summary

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

The NM_006398.4(UBD):c.198T>C(p.Tyr66Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 1,613,028 control chromosomes in the GnomAD database, including 8,318 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 0.053 ( 363 hom., cov: 32)

Exomes 𝑓: 0.092 ( 7955 hom. )

Consequence

UBD
NM_006398.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

30 publications found

Variant links:

Genes affected

UBD (HGNC:18795): (ubiquitin D) This gene encodes a protein which contains two ubiquitin-like domains and appears to have similar function to ubiquitin. Through covalent attachment, the encoded protein targets other proteins for 26S proteasome degradation. This protein has been implicated to function in many cellular processes, including caspase-dependent apoptosis, formation of aggresomes, mitotic regulation, and dendritic cell maturation. Upregulation of this gene may promote inflammation in chronic kidney disease and has been observed in many cancer types. [provided by RefSeq, Aug 2017]

UBD links:

OR2I1 (HGNC:8258): (olfactory receptor family 2 subfamily I member 1 pseudogene) 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]

OR2I1 links:

GABBR1 (HGNC:4070): (gamma-aminobutyric acid type B receptor subunit 1) This gene encodes a receptor for gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the mammalian central nervous system. This receptor functions as a heterodimer with GABA(B) receptor 2. Defects in this gene may underlie brain disorders such as schizophrenia and epilepsy. Alternative splicing generates multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jan 2016]

GABBR1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with language delay and variable cognitive abnormalities
Inheritance: AD Classification: MODERATE Submitted by: G2P

GABBR1 links:

Genome browser will be placed here

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=-0.79).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBD	NM_006398.4 link	c.198T>C	p.Tyr66Tyr	synonymous_variant	Exon 2 of 2	ENST00000377050.5	NP_006389.2
OR2I1	NM_001396058.1 link	c.*2014A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000641137.2	NP_001382987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBD	ENST00000377050.5 link	c.198T>C	p.Tyr66Tyr	synonymous_variant	Exon 2 of 2	1	NM_006398.4	ENSP00000366249.4
OR2I1P	ENST00000641137.2 link	c.*2014A>G		3_prime_UTR_variant	Exon 2 of 2		NM_001396058.1	ENSP00000493715.1

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8113

AN:

152160

Hom.:

363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.0215

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0420

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0945

Gnomad OTH

AF:

0.0360

GnomAD2 exomes

AF:

0.0494

AC:

12192

AN:

246602

AF XY:

0.0495

show subpopulations

Gnomad AFR exome

AF:

0.0165

Gnomad AMR exome

AF:

0.0154

Gnomad ASJ exome

AF:

0.0250

Gnomad EAS exome

AF:

0.0000548

Gnomad FIN exome

AF:

0.0416

Gnomad NFE exome

AF:

0.0901

Gnomad OTH exome

AF:

0.0471

GnomAD4 exome

AF:

0.0925

AC:

135090

AN:

1460750

Hom.:

7955

Cov.:

AF XY:

0.0891

AC XY:

64747

AN XY:

726686

show subpopulations

African (AFR)

AF:

0.0144

AC:

482

AN:

33478

American (AMR)

AF:

0.0158

AC:

706

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0263

AC:

688

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.000151

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0437

AC:

2286

AN:

52318

Middle Eastern (MID)

AF:

0.00381

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.114

AC:

126377

AN:

1111986

Other (OTH)

AF:

0.0747

AC:

4512

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

7459

14918

22377

29836

37295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4666

9332

13998

18664

23330

<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:

0.0533

AC:

8109

AN:

152278

Hom.:

363

Cov.:

AF XY:

0.0473

AC XY:

3521

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0151

AC:

626

AN:

41574

American (AMR)

AF:

0.0214

AC:

328

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0239

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0420

AC:

446

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0944

AC:

6422

AN:

68000

Other (OTH)

AF:

0.0356

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

392

785

1177

1570

1962

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0823

Hom.:

2023

Bravo

AF:

0.0506

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.0883

EpiControl

AF:

0.0819

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.33

(source)

DANN

Benign

0.80

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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