rs404240

Variant names:

• chr6-29556180-A-G
• rs404240
• NM_006398.4:c.198T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-29556180-A-G
• chr6-29556180-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 30 publications found

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]

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]

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

ACMG classification

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	c.198T>C	p.Tyr66Tyr	synonymous_variant	Exon 2 of 2	ENST00000377050.5	NP_006389.2
OR2I1	NM_001396058.1	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	c.198T>C	p.Tyr66Tyr	synonymous_variant	Exon 2 of 2	1	NM_006398.4	ENSP00000366249.4
OR2I1P	ENST00000641137.2	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.: 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

GnomAD2 exomes AF: 0.0494 AC: 12192 AN: 246602 AF XY: 0.0495

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

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: 4 AN: 39700

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86256

European-Finnish (FIN) AF: 0.0437 AC: 2286 AN: 52318

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.114 AC: 126377 AN: 1111986

Other (OTH) AF: 0.0747 AC: 4512 AN: 60386

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

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: 83 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.0420 AC: 446 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0944 AC: 6422 AN: 68000

Other (OTH) AF: 0.0356 AC: 75 AN: 2106

Alfa AF: 0.0823 Hom.: 2023

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
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs404240; hg19: chr6-29523957;