rs404240

chr6-29556180-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006398.4(UBD):c.198T>C(p.Tyr66=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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]

OR2I1P (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]

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
UBD	NM_006398.4	c.198T>C	p.Tyr66=	synonymous_variant	2/2	ENST00000377050.5
OR2I1P	NM_001396058.1	c.*2014A>G		3_prime_UTR_variant	2/2	ENST00000641137.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBD	ENST00000377050.5	c.198T>C	p.Tyr66=	synonymous_variant	2/2	1	NM_006398.4	P1
OR2I1P	ENST00000641137.2	c.*2014A>G		3_prime_UTR_variant	2/2		NM_001396058.1	P1

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8113 AN: 152160 Hom.: 363 Cov.: 32

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

GnomAD3 exomes AF: 0.0494 AC: 12192 AN: 246602 Hom.: 530 AF XY: 0.0495 AC XY: 6647 AN XY: 134390

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 SAS exome AF: 0.0000329

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.: 37 AF XY: 0.0891 AC XY: 64747 AN XY: 726686

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.0158

Gnomad4 ASJ exome AF: 0.0263

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.0437

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.0747

GnomAD4 genome AF: 0.0533 AC: 8109 AN: 152278 Hom.: 363 Cov.: 32 AF XY: 0.0473 AC XY: 3521 AN XY: 74450

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.0214

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0420

Gnomad4 NFE AF: 0.0944

Gnomad4 OTH AF: 0.0356

Alfa AF: 0.0810 Hom.: 600

Bravo AF: 0.0506

Asia WGS AF: 0.00318 AC: 12 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
Dann	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs404240; hg19: chr6-29523957;