rs6298

chr6-77463275-G-Achr6-77463275-G-Cchr6-77463275-G-T

Variant summary

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

The NM_000863.3(HTR1B):c.129C>T(p.Ser43=) 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 1,613,886 control chromosomes in the GnomAD database, including 64,085 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 (6051 hom., cov: 32)
  • Exomes 𝑓: 0.28 (58034 hom.)
• Consequence: HTR1B NM_000863.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.588

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=-0.73).
• BP7: Synonymous conserved (PhyloP=0.588 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR1B	NM_000863.3	c.129C>T	p.Ser43=	synonymous_variant	1/1	ENST00000369947.5
LOC105377864	XM_047419660.1	c.-3742-11251G>A		intron_variant
LOC105377864	XM_047419659.1	c.-11184G>A		5_prime_UTR_variant	2/6
LOC105377864	XM_047419661.1	c.-3917+157G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR1B	ENST00000369947.5	c.129C>T	p.Ser43=	synonymous_variant	1/1		NM_000863.3	P1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41737 AN: 152016 Hom.: 6055 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.273

GnomAD3 exomes AF: 0.312 AC: 78496 AN: 251480 Hom.: 13254 AF XY: 0.310 AC XY: 42097 AN XY: 135912

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: 0.351

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.277 AC: 404461 AN: 1461752 Hom.: 58034 Cov.: 38 AF XY: 0.278 AC XY: 202181 AN XY: 727184

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: 0.354

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.274 AC: 41747 AN: 152134 Hom.: 6051 Cov.: 32 AF XY: 0.279 AC XY: 20727 AN XY: 74378

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.274

Alfa AF: 0.262 Hom.: 10794

Bravo AF: 0.283

Asia WGS AF: 0.395 AC: 1369 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	-0.73
Cadd	Benign	8.5
Dann	Benign	0.73

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: rs6298; hg19: chr6-78172992; COSMIC: COSV64051193;