NM_000863.3:c.861G>C

Variant names:

• chr6-77462543-C-G
• rs6296
• NM_000863.3:c.861G>C
• HTR1B p.Val287Val

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

-8 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -8 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_StrongB4_Strong

The NM_000863.3(HTR1B):c.861G>C (p.Val287Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.276 (AC=445,623) in the gnomAD database across 1,613,186 control chromosomes, including 63,939 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.482. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The variant has been observed in cBioPortal in 3 samples across 3 studies and 3 cancer types; somatic enrichment level: SUPPORTING_LOW (Observed in a small number of cBioPortal cases.).

• 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
• Publications: 91 publications found

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:):

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Benign. The variant received -8 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.482 — exceeds 1% threshold (B1 applied)
	B4Synonymous/intronic, no splicing impact		Synonymous/intronic variant with confirmed no splicing impact (B4 strong); Synonymous variant — splicing algorithms confirm no impact on splicing (B4 strong [-4])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000863.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	HTR1B NM_000863.3	MANE Select	c.861G>C p.Val287Val	synonymous	Exon 1 of 1	Prot: NP_000854.1 UniProt:

HTR1B NM_000863.3

MANE Select

HGVSc / HGVSpc.861G>Cp.Val287Val

Exon rankExon 1 of 1

synonymous

Prot: NP_000854.1UniProt: P28222X5D7I5

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	HTR1B ENST00000369947.5	TSL:6MANE Select	c.861G>C p.Val287Val	synonymous	Exon 1 of 1	Prot: ENSP00000358963.3 UniProt:
	ENSG00000296734 ENST00000741460.1		n.48+4357G>C	intron	Intron 1 of 3	Prot:

HTR1B ENST00000369947.5

TSL:6MANE Select

HGVSc / HGVSpc.861G>Cp.Val287Val

Exon rankExon 1 of 1

synonymous

Prot: ENSP00000358963.3UniProt: P28222

ENSG00000296734 ENST00000741460.1

HGVSc / HGVSpn.48+4357G>C

Exon rankIntron 1 of 3

intron

Prot:

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.274	AC:41648	Hom:6038	AN:151758	Cov:31
GnomAD2 exomes	AF: 0.312	AC:78305	Hom:	AN:251170	Cov:
GnomAD4 exome	AF: 0.276	AC:403965	Hom:57905	AN:1461310	Cov:40
GnomAD4 genome	AF: 0.274	AC:41658	Hom:6034	AN:151876	Cov:31
TOPMed (Bravo)	AF: 0.283	AC:74908	Hom:11241	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.263	AC:14950	Hom:2021	AN:56744	Cov:
Local & regional cohorts 11 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.266	AC:624	Hom:85	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.509	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.297	AC:89	Hom:	AN:300	Cov:
ESP6500 (Exome Variant Server)	AF: 0.249	AC:3244	Hom:	AN:13006	Cov:
GenomeAsia100K	AF: 0.393	AC:1364	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.477	AC:3454	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.246	AC:495	Hom:	AN:2010	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.452	AC:55488	Hom:12524	AN:122816	Cov:
Turkish Variome	AF: 0.288	AC:1918	Hom:307	AN:6652	Cov:
UK10K	AF: 0.259	AC:1958	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.510	AC:4570	Hom:1210	AN:8960	Cov:

Showing 17 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.274 *	3026	11050	0.276 *	4845	17572
BipEx(Bipolar disorder (including schizoaffective))	0.272	7717	28420	0.272	7840	28844
Epi25(Epilepsy)	0.282	11846	41958	0.283	18909	66888
SCHEMA(Schizophrenia)	0.338	50672	150008	0.336	81965	243992

Showing 4 cohortsAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	17
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.88
GPN-Star LLR	N/A	-3.3
GPN-Star score	N/A	3.3
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	0.30

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.020	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs6296;

hg19: chr6-78172260;

COSMIC: COSV64051114;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar