Variant 5-148550246-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000870.7(HTR4):c.43G>A(p.Gly15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000482 in 1,614,020 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 3 hom. )

Consequence

HTR4
NM_000870.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.359

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005935043).

BP6

Variant 5-148550246-C-T is Benign according to our data. Variant chr5-148550246-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 709214.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR4	NM_000870.7 linkuse as main transcript	c.43G>A	p.Gly15Arg	missense_variant	3/7	ENST00000377888.8
LOC107986462	XR_001742935.2 linkuse as main transcript	n.603C>T		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR4	ENST00000377888.8 linkuse as main transcript	c.43G>A	p.Gly15Arg	missense_variant	3/7	1	NM_000870.7		Q13639-1

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

342

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00768

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.000724

AC:

182

AN:

251308

Hom.:

AF XY:

0.000530

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00812

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000299

AC:

437

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

190

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00759

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.000811

GnomAD4 genome

AF:

0.00224

AC:

341

AN:

152184

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

165

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00764

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000341

Hom.:

Bravo

AF:

0.00254

ESP6500AA

AF:

0.00726

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000807

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.86

D;D;D;D;.;.;D;D

M_CAP

Benign

0.0063

MetaRNN

Benign

0.0059

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;N;N;N;N;N;N;N

MutationTaster

Benign

0.93

N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.37

N;N;N;N;N;N;N;.

REVEL

Benign

0.024

Sift

Benign

0.20

T;T;T;T;T;T;T;.

Sift4G

Benign

0.41

T;T;T;T;T;T;T;T

Polyphen

0.0090

B;.;B;.;B;.;.;B

Vest4

0.17

MutPred

0.33

Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);Gain of solvent accessibility (P = 0.0674);

MVP

0.17

MPC

0.26

ClinPred

0.018

GERP RS

1.1

Varity_R

0.064

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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