Variant rs130060 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000863.3(HTR1B):c.371T>G(p.Phe124Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,614,186 control chromosomes in the GnomAD database, including 170 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0091 ( 7 hom., cov: 32)

Exomes 𝑓: 0.013 ( 163 hom. )

Consequence

HTR1B
NM_000863.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.32

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012479603).

BS2

High AC in GnomAd4 at 1387 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HTR1B	NM_000863.3 linkuse as main transcript	c.371T>G	p.Phe124Cys	missense_variant	1/1	ENST00000369947.5
LOC105377864	XM_047419660.1 linkuse as main transcript	c.-3742-11493A>C		intron_variant
LOC105377864	XM_047419659.1 linkuse as main transcript	c.-11426A>C		5_prime_UTR_variant	2/6
LOC105377864	XM_047419661.1 linkuse as main transcript	c.-4002A>C		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR1B	ENST00000369947.5 linkuse as main transcript	c.371T>G	p.Phe124Cys	missense_variant	1/1		NM_000863.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00911

AC:

1386

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00706

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0143

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00994

AC:

2498

AN:

251286

Hom.:

AF XY:

0.00991

AC XY:

1346

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00885

Gnomad ASJ exome

AF:

0.0149

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00575

Gnomad FIN exome

AF:

0.00924

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.0131

AC:

19138

AN:

1461868

Hom.:

163

Cov.:

AF XY:

0.0128

AC XY:

9305

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00212

Gnomad4 AMR exome

AF:

0.00874

Gnomad4 ASJ exome

AF:

0.0159

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00654

Gnomad4 FIN exome

AF:

0.00908

Gnomad4 NFE exome

AF:

0.0148

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.00911

AC:

1387

AN:

152318

Hom.:

Cov.:

AF XY:

0.00827

AC XY:

616

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00706

Gnomad4 NFE

AF:

0.0142

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.0130

Hom.:

Bravo

AF:

0.00908

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0117

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0135

AC:

116

ExAC

AF:

0.00925

AC:

1123

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0142

EpiControl

AF:

0.0139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.86

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.6

REVEL

Benign

0.12

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

0.67

Vest4

0.56

MVP

0.44

MPC

1.5

ClinPred

0.033

GERP RS

5.3

Varity_R

0.38

gMVP

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over