Genetic Variant HTR1B:p.Val287Val (chr6-77462543-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is The variant received 1 classification points (ACMG Germline Pathogenicity v2019). PM2BP7

The NM_000863.3(HTR1B):c.861G>A (p.Val287Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Consequence

HTR1B
NM_000863.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.298

Publications

0 publications found

Variant links:

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]

HTR1B links:

LOC105377864 (HGNC:):

LOC105377864 links:

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new If you want to explore the variant's impact on the transcript NM_000863.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

Show applied only (2)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.
	BP7Synonymous variant, no splicing impact		Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).

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>A p.Val287Val	synonymous	Exon 1 of 1	Prot: NP_000854.1 UniProt: P28222X5D7I5

HTR1B NM_000863.3

MANE Select

HGVSc / HGVSpc.861G>Ap.Val287Val

Exon rankExon 1 of 1

synonymous

Prot: NP_000854.1UniProt: P28222

X5D7I5

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	HTR1B ENST00000369947.5	TSL:6MANE Select	c.861G>A p.Val287Val	synonymous	Exon 1 of 1	Prot: ENSP00000358963.3 UniProt: P28222
	ENSG00000296734 ENST00000741460.1		n.48+4357G>A	intron	Intron 1 of 3	Prot:

HTR1B ENST00000369947.5

TSL:6MANE Select

HGVSc / HGVSpc.861G>Ap.Val287Val

Exon rankExon 1 of 1

synonymous

Prot: ENSP00000358963.3UniProt: P28222

ENSG00000296734 ENST00000741460.1

HGVSc / HGVSpn.48+4357G>A

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 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:31
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:40
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:31

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score
AlphaGenome AVI	Uncertain	16
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.95
GPN-Star LLR	N/A	-2.7
GPN-Star score	N/A	2.7
PhyloP100	Benign	0.30

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
DS_DG_spliceai	Uncertain	0.22	Position offset: 7
Pangolin (max)	Benign	0.010
SpliceAI score (max)	Uncertain	0.22	Details are displayed if max score is > 0.2

Showing 3 of 3 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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence