rs6296

chr6-77462543-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000863.3(HTR1B):c.861G>C(p.Val287=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,613,186 control chromosomes in the GnomAD database, including 63,939 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 0.27 (6034 hom., cov: 31)
  • Exomes 𝑓: 0.28 (57905 hom.)
• Consequence: HTR1B NM_000863.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298

Genes affected

HTR1B (HGNC:5287): (5-hydroxytryptamine receptor 1B) The protein encoded by this intronless gene is a G-protein coupled receptor for serotonin (5-hydroxytryptamine). Ligand binding activates second messengers that inhibit the activity of adenylate cyclase and manage the release of serotonin, dopamine, and acetylcholine in the brain. The encoded protein may be involved in several neuropsychiatric disorders and therefore is often a target of antidepressant and other psychotherapeutic drugs. [provided by RefSeq, Nov 2015]

LOC105377864 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.298 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR1B	NM_000863.3	c.861G>C	p.Val287=	synonymous_variant	1/1	ENST00000369947.5
LOC105377864	XM_047419660.1	c.-3742-11983C>G		intron_variant
LOC105377864	XM_047419659.1	c.-11681C>G		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR1B	ENST00000369947.5	c.861G>C	p.Val287=	synonymous_variant	1/1		NM_000863.3	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41648 AN: 151758 Hom.: 6038 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.274

GnomAD3 exomes AF: 0.312 AC: 78305 AN: 251170 Hom.: 13200 AF XY: 0.309 AC XY: 41991 AN XY: 135784

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.431

Gnomad ASJ exome AF: 0.249

Gnomad EAS exome AF: 0.500

Gnomad SAS exome AF: 0.347

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.276 AC: 403965 AN: 1461310 Hom.: 57905 Cov.: 40 AF XY: 0.278 AC XY: 201882 AN XY: 726962

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.249

Gnomad4 EAS exome AF: 0.476

Gnomad4 SAS exome AF: 0.350

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.274 AC: 41658 AN: 151876 Hom.: 6034 Cov.: 31 AF XY: 0.278 AC XY: 20659 AN XY: 74218

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.275

Alfa AF: 0.265 Hom.: 1822

Bravo AF: 0.283

Asia WGS AF: 0.393 AC: 1364 AN: 3478

EpiCase AF: 0.263

EpiControl AF: 0.256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	12
Dann	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6296; hg19: chr6-78172260; COSMIC: COSV64051114;