6-29588982-C-T

Variant names:

• chr6-29588982-C-T
• rs362521
• NM_007160.4:c.*99C>T

Variant summary

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

The NM_007160.4(OR2H2):​c.*99C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 649,122 control chromosomes in the GnomAD database, including 1,691 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 0.050 (249 hom., cov: 32)
  • Exomes 𝑓: 0.067 (1442 hom.)
• Consequence: OR2H2 NM_007160.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 19 publications found

Genes affected

OR2H2 (HGNC:8253): (olfactory receptor family 2 subfamily H member 2) 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007160.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2H2	NM_007160.4	MANE Select	c.*99C>T		3_prime_UTR	Exon 2 of 2	NP_009091.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2H2	ENST00000641840.1	MANE Select	c.*99C>T		3_prime_UTR	Exon 2 of 2	ENSP00000492959.1	O95918
	GABBR1	ENST00000355973.7	TSL:2	c.*2+14559G>A		intron	N/A	ENSP00000348248.3	Q9UBS5-2
	OR2H2	ENST00000383640.4	TSL:6	c.*99C>T		downstream_gene	N/A	ENSP00000373136.2	O95918

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7584 AN: 152150 Hom.: 251 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.0984

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0581

Gnomad OTH AF: 0.0606

GnomAD4 exome AF: 0.0665 AC: 33045 AN: 496854 Hom.: 1442 Cov.: 0 AF XY: 0.0710 AC XY: 18738 AN XY: 263804

African (AFR) AF: 0.0216 AC: 297 AN: 13762

American (AMR) AF: 0.0680 AC: 1617 AN: 23770

Ashkenazi Jewish (ASJ) AF: 0.0861 AC: 1272 AN: 14766

East Asian (EAS) AF: 0.0747 AC: 2413 AN: 32316

South Asian (SAS) AF: 0.137 AC: 6746 AN: 49270

European-Finnish (FIN) AF: 0.0259 AC: 1173 AN: 45354

Middle Eastern (MID) AF: 0.110 AC: 405 AN: 3686

European-Non Finnish (NFE) AF: 0.0601 AC: 17195 AN: 286178

Other (OTH) AF: 0.0694 AC: 1927 AN: 27752

GnomAD4 genome AF: 0.0498 AC: 7582 AN: 152268 Hom.: 249 Cov.: 32 AF XY: 0.0506 AC XY: 3765 AN XY: 74466

African (AFR) AF: 0.0215 AC: 894 AN: 41550

American (AMR) AF: 0.0532 AC: 814 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0841 AC: 292 AN: 3470

East Asian (EAS) AF: 0.0982 AC: 509 AN: 5182

South Asian (SAS) AF: 0.132 AC: 638 AN: 4828

European-Finnish (FIN) AF: 0.0281 AC: 298 AN: 10606

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0581 AC: 3953 AN: 68020

Other (OTH) AF: 0.0614 AC: 130 AN: 2116

Alfa AF: 0.0568 Hom.: 790

Bravo AF: 0.0498

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.098
DANN	Benign	0.49
PhyloP100		-2.2
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: rs362521; hg19: chr6-29556759;