1-19666020-C-T

Variant names:

• chr1-19666020-C-T
• rs1805054
• NM_000871.3:c.267C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_000871.3(HTR6):​c.267C>T​(p.Tyr89Tyr) 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
• Publications: 66 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HTR6	NM_000871.3	c.267C>T	p.Tyr89Tyr	synonymous_variant	Exon 1 of 3	ENST00000289753.2	NP_000862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR6	ENST00000289753.2	c.267C>T	p.Tyr89Tyr	synonymous_variant	Exon 1 of 3	1	NM_000871.3	ENSP00000289753.1

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

GnomAD2 exomes AF: 0.146 AC: 36611 AN: 250026 AF XY: 0.147

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 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

African (AFR) AF: 0.201 AC: 6711 AN: 33468

American (AMR) AF: 0.116 AC: 5171 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 4327 AN: 26106

East Asian (EAS) AF: 0.262 AC: 10416 AN: 39690

South Asian (SAS) AF: 0.160 AC: 13780 AN: 86246

European-Finnish (FIN) AF: 0.111 AC: 5900 AN: 53194

Middle Eastern (MID) AF: 0.160 AC: 925 AN: 5768

European-Non Finnish (NFE) AF: 0.132 AC: 146629 AN: 1111828

Other (OTH) AF: 0.139 AC: 8419 AN: 60378

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

African (AFR) AF: 0.194 AC: 8074 AN: 41554

American (AMR) AF: 0.124 AC: 1903 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3468

East Asian (EAS) AF: 0.218 AC: 1127 AN: 5168

South Asian (SAS) AF: 0.180 AC: 872 AN: 4832

European-Finnish (FIN) AF: 0.113 AC: 1198 AN: 10622

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9655 AN: 68024

Other (OTH) AF: 0.153 AC: 324 AN: 2114

Alfa AF: 0.146 Hom.: 3201

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
PhyloP100		0.47
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: rs1805054; hg19: chr1-19992513; COSMIC: COSV57032031;