1-19666992-A-G

Position:

• chr1-19666992-A-G

Variant summary

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

The NM_000871.3(HTR6):​c.714+525A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 151,764 control chromosomes in the GnomAD database, including 46,288 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 0.78 (46288 hom., cov: 29)
• Consequence: HTR6 NM_000871.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR6	NM_000871.3	c.714+525A>G		intron_variant		ENST00000289753.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR6	ENST00000289753.2	c.714+525A>G		intron_variant		1	NM_000871.3	P1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118041 AN: 151646 Hom.: 46240 Cov.: 29

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.779 AC: 118149 AN: 151764 Hom.: 46288 Cov.: 29 AF XY: 0.774 AC XY: 57435 AN XY: 74182

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.706

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.758

Alfa AF: 0.786 Hom.: 16393

Bravo AF: 0.772

Asia WGS AF: 0.641 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.19
DANN	Benign	0.57

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: rs4912138; hg19: chr1-19993485;