dbSNP rs6296: HTR1B:p.Val287Val (chr6-77462543-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.298

Publications

212 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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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000863.3. You can select a different transcript below to see updated ACMG 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	NP_000854.1	P28222

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41648

AN:

151758

Hom.:

6038

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.312

AC:

78305

AN:

251170

AF XY:

0.309

show subpopulations

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 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.:

AF XY:

0.278

AC XY:

201882

AN XY:

726962

show subpopulations

African (AFR)

AF:

0.230

AC:

7694

AN:

33480

American (AMR)

AF:

0.426

AC:

19055

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

6516

AN:

26136

East Asian (EAS)

AF:

0.476

AC:

18883

AN:

39700

South Asian (SAS)

AF:

0.350

AC:

30213

AN:

86258

European-Finnish (FIN)

AF:

0.252

AC:

13354

AN:

52924

Middle Eastern (MID)

AF:

0.257

AC:

1485

AN:

5768

European-Non Finnish (NFE)

AF:

0.261

AC:

289680

AN:

1111934

Other (OTH)

AF:

0.283

AC:

17085

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

18891

37782

56672

75563

94454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9976

19952

29928

39904

49880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.274

AC:

41658

AN:

151876

Hom.:

6034

Cov.:

AF XY:

0.278

AC XY:

20659

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.232

AC:

9616

AN:

41392

American (AMR)

AF:

0.381

AC:

5801

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

876

AN:

3470

East Asian (EAS)

AF:

0.498

AC:

2559

AN:

5140

South Asian (SAS)

AF:

0.341

AC:

1636

AN:

4792

European-Finnish (FIN)

AF:

0.243

AC:

2575

AN:

10578

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.260

AC:

17647

AN:

67948

Other (OTH)

AF:

0.275

AC:

580

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1504

3008

4512

6016

7520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over