rs1805054

Positions:

• chr1-19666020-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000871.3(HTR6):​c.267C>T​(p.Tyr89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,613,676 control chromosomes in the GnomAD database, including 16,930 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 0.16 (1997 hom., cov: 33)
  • Exomes 𝑓: 0.14 (14933 hom.)
• Consequence: HTR6 NM_000871.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469

Genes affected

HTR6 (HGNC:5301): (5-hydroxytryptamine receptor 6) This gene encodes a protein that belongs to the seven-transmembrane G protein-coupled receptor family of proteins. The encoded protein couples with the Gs alpha subunit and stimulates adenylate cyclase to activate the cyclic AMP-dependent signaling pathway. This receptor is thought to regulate cholinergic neuronal transmission in the brain. Several antidepressants and antipsychotic drugs have a high affinity for this receptor. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=0.469 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR6	NM_000871.3	c.267C>T	p.Tyr89=	synonymous_variant	1/3	ENST00000289753.2	NP_000862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR6	ENST00000289753.2	c.267C>T	p.Tyr89=	synonymous_variant	1/3	1	NM_000871.3	ENSP00000289753	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24011 AN: 152176 Hom.: 1996 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.154

GnomAD3 exomes AF: 0.146 AC: 36611 AN: 250026 Hom.: 2873 AF XY: 0.147 AC XY: 19856 AN XY: 135382

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.223

Gnomad SAS exome AF: 0.163

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.138 AC: 202278 AN: 1461382 Hom.: 14933 Cov.: 34 AF XY: 0.140 AC XY: 101789 AN XY: 727048

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.158 AC: 24026 AN: 152294 Hom.: 1997 Cov.: 33 AF XY: 0.158 AC XY: 11797 AN XY: 74468

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.153

Alfa AF: 0.146 Hom.: 1947

Bravo AF: 0.161

Asia WGS AF: 0.192 AC: 667 AN: 3478

EpiCase AF: 0.145

EpiControl AF: 0.139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.7
DANN	Benign	0.96

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: rs1805054; hg19: chr1-19992513; COSMIC: COSV57032031;