1-19676025-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.715-2542C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,790 control chromosomes in the GnomAD database, including 24,574 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 0.56 (24574 hom., cov: 30)
• Consequence: HTR6 NM_000871.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR6	NM_000871.3	c.715-2542C>T		intron_variant		ENST00000289753.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR6	ENST00000289753.2	c.715-2542C>T		intron_variant		1	NM_000871.3	P1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84959 AN: 151670 Hom.: 24578 Cov.: 30

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.560 AC: 84979 AN: 151790 Hom.: 24574 Cov.: 30 AF XY: 0.556 AC XY: 41215 AN XY: 74166

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.540

Alfa AF: 0.616 Hom.: 49804

Bravo AF: 0.543

Asia WGS AF: 0.377 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.1
Dann	Benign	0.53

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: rs9659997; hg19: chr1-20002518;