Variant 5-63961168-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

The NM_000524.4(HTR1A):c.552C>T(p.Pro184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,614,156 control chromosomes in the GnomAD database, including 338 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 0.019 ( 52 hom., cov: 33)

Exomes 𝑓: 0.018 ( 286 hom. )

Consequence

HTR1A
NM_000524.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.541

Variant links:

Genes affected

HTR1A (HGNC:5286): (5-hydroxytryptamine receptor 1A) This gene encodes a G protein-coupled receptor for 5-hydroxytryptamine (serotonin), and belongs to the 5-hydroxytryptamine receptor subfamily. Serotonin has been implicated in a number of physiologic processes and pathologic conditions. Inactivation of this gene in mice results in behavior consistent with an increased anxiety and stress response. Mutation in the promoter of this gene has been associated with menstrual cycle-dependent periodic fevers. [provided by RefSeq, Jun 2012]

HTR1A links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP7

Synonymous conserved (PhyloP=0.541 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0189 (2884/152336) while in subpopulation EAS AF= 0.0356 (184/5164). AF 95% confidence interval is 0.0314. There are 52 homozygotes in gnomad4. There are 1405 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2884 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR1A	NM_000524.4 linkuse as main transcript	c.552C>T	p.Pro184=	synonymous_variant	1/1	ENST00000323865.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR1A	ENST00000323865.5 linkuse as main transcript	c.552C>T	p.Pro184=	synonymous_variant	1/1		NM_000524.4	P1
	ENST00000502882.1 linkuse as main transcript	n.97-3153C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2881

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0286

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.0355

Gnomad SAS

AF:

0.0304

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0167

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.0197

AC:

4905

AN:

249262

Hom.:

AF XY:

0.0204

AC XY:

2747

AN XY:

134850

show subpopulations

Gnomad AFR exome

AF:

0.0176

Gnomad AMR exome

AF:

0.0189

Gnomad ASJ exome

AF:

0.0161

Gnomad EAS exome

AF:

0.0370

Gnomad SAS exome

AF:

0.0329

Gnomad FIN exome

AF:

0.00402

Gnomad NFE exome

AF:

0.0170

Gnomad OTH exome

AF:

0.0208

GnomAD4 exome

AF:

0.0181

AC:

26492

AN:

1461820

Hom.:

286

Cov.:

AF XY:

0.0185

AC XY:

13443

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0185

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.0147

Gnomad4 EAS exome

AF:

0.0314

Gnomad4 SAS exome

AF:

0.0317

Gnomad4 FIN exome

AF:

0.00358

Gnomad4 NFE exome

AF:

0.0172

Gnomad4 OTH exome

AF:

0.0190

GnomAD4 genome

AF:

0.0189

AC:

2884

AN:

152336

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

1405

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0177

Gnomad4 AMR

AF:

0.0287

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.0356

Gnomad4 SAS

AF:

0.0305

Gnomad4 FIN

AF:

0.00320

Gnomad4 NFE

AF:

0.0167

Gnomad4 OTH

AF:

0.0236

Alfa

AF:

0.0172

Hom.:

Bravo

AF:

0.0219

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0190

EpiControl

AF:

0.0188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.1

DANN

Benign

0.91

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