1-19676025-C-T

Variant names:

• chr1-19676025-C-T
• rs9659997
• NM_000871.3:c.715-2542C>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.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
• Publications: 12 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=-0.82).
• 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 rank	MANE	Protein	UniProt
HTR6	NM_000871.3	c.715-2542C>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.715-2542C>T		intron_variant	Intron 1 of 2	1	NM_000871.3	ENSP00000289753.1

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

African (AFR) AF: 0.457 AC: 18919 AN: 41354

American (AMR) AF: 0.516 AC: 7856 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2103 AN: 3466

East Asian (EAS) AF: 0.209 AC: 1083 AN: 5170

South Asian (SAS) AF: 0.522 AC: 2502 AN: 4790

European-Finnish (FIN) AF: 0.688 AC: 7241 AN: 10526

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43623 AN: 67934

Other (OTH) AF: 0.540 AC: 1139 AN: 2108

Alfa AF: 0.604 Hom.: 77285

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
PhyloP100		-0.087
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: rs9659997; hg19: chr1-20002518;