Variant 5-148483255-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000870.7(HTR4):c.1115G>A(p.Cys372Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 1,613,852 control chromosomes in the GnomAD database, including 245 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.022 ( 127 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 118 hom. )

Consequence

HTR4
NM_000870.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.564

Variant links:

Genes affected

HTR4 (HGNC:5299): (5-hydroxytryptamine receptor 4) This gene is a member of the family of serotonin receptors, which are G protein coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described. [provided by RefSeq, May 2010]

HTR4 links:

LOC107986462 (HGNC:):

LOC107986462 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015491247).

BP6

Variant 5-148483255-C-T is Benign according to our data. Variant chr5-148483255-C-T is described in ClinVar as [Benign]. Clinvar id is 776075.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR4	NM_000870.7 linkuse as main transcript	c.1115G>A	p.Cys372Tyr	missense_variant	7/7	ENST00000377888.8
LOC107986462	XR_001742935.2 linkuse as main transcript	n.441+14238C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR4	ENST00000377888.8 linkuse as main transcript	c.1115G>A	p.Cys372Tyr	missense_variant	7/7	1	NM_000870.7		Q13639-1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3315

AN:

152054

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0754

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00897

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00557

AC:

1394

AN:

250384

Hom.:

AF XY:

0.00397

AC XY:

537

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.0749

Gnomad AMR exome

AF:

0.00316

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000850

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00410

GnomAD4 exome

AF:

0.00223

AC:

3255

AN:

1461680

Hom.:

118

Cov.:

AF XY:

0.00191

AC XY:

1388

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.0773

Gnomad4 AMR exome

AF:

0.00367

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000951

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000603

Gnomad4 OTH exome

AF:

0.00548

GnomAD4 genome

AF:

0.0219

AC:

3332

AN:

152172

Hom.:

127

Cov.:

AF XY:

0.0209

AC XY:

1556

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0756

Gnomad4 AMR

AF:

0.00896

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00702

Hom.:

Bravo

AF:

0.0254

ESP6500AA

AF:

0.0713

AC:

314

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00680

AC:

826

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.10

T;.;.;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.47

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

N;.;.;N

MutationTaster

Benign

0.72

D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.010

N;N;.;.

REVEL

Benign

0.14

Sift

Benign

0.31

T;D;.;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.21

B;.;.;B

Vest4

0.065

MVP

0.24

MPC

0.36

ClinPred

0.020

GERP RS

2.6

Varity_R

0.072

gMVP

0.19

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over