rs3790756

Positions:

• chr1-19669739-C-T

Variant summary

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

The NM_000871.3(HTR6):​c.714+3272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,200 control chromosomes in the GnomAD database, including 1,442 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 0.13 (1442 hom., cov: 31)
• Consequence: HTR6 NM_000871.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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.714+3272C>T		intron_variant		ENST00000289753.2	NP_000862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR6	ENST00000289753.2	c.714+3272C>T		intron_variant		1	NM_000871.3	ENSP00000289753	P1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20500 AN: 152082 Hom.: 1441 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.138

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.135 AC: 20517 AN: 152200 Hom.: 1442 Cov.: 31 AF XY: 0.136 AC XY: 10156 AN XY: 74416

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.138

Alfa AF: 0.142 Hom.: 950

Bravo AF: 0.134

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.71

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: rs3790756; hg19: chr1-19996232;