1-19671415-C-T

Variant names:

• chr1-19671415-C-T
• rs3790757
• NM_000871.3:c.714+4948C>T

Variant summary

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

The NM_000871.3(HTR6):​c.714+4948C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0375 in 152,240 control chromosomes in the GnomAD database, including 270 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 0.037 (270 hom., cov: 31)
• Consequence: HTR6 NM_000871.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.956
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR6	NM_000871.3	c.714+4948C>T		intron_variant	Intron 1 of 2	ENST00000289753.2	NP_000862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR6	ENST00000289753.2	c.714+4948C>T		intron_variant	Intron 1 of 2	1	NM_000871.3	ENSP00000289753.1

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5696 AN: 152122 Hom.: 264 Cov.: 31

Gnomad AFR AF: 0.00775

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0268

Gnomad OTH AF: 0.0311

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

GnomAD4 genome AF: 0.0375 AC: 5706 AN: 152240 Hom.: 270 Cov.: 31 AF XY: 0.0414 AC XY: 3083 AN XY: 74464

African (AFR) AF: 0.00773 AC: 321 AN: 41542

American (AMR) AF: 0.114 AC: 1739 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.175 AC: 908 AN: 5176

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4830

European-Finnish (FIN) AF: 0.0662 AC: 702 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0268 AC: 1824 AN: 68004

Other (OTH) AF: 0.0303 AC: 64 AN: 2110

Alfa AF: 0.0321 Hom.: 207

Bravo AF: 0.0397

Asia WGS AF: 0.0940 AC: 325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.69
PhyloP100		-0.96
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: rs3790757; hg19: chr1-19997908;