dbSNP rs34118353: HTR1A:p.Pro184Pro (chr5-63961168-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

The NM_000524.4(HTR1A):c.552C>T(p.Pro184Pro) 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

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

menstrual cycle-dependent periodic fever
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

HTR1A links:

ENSG00000248285 (HGNC:):

ENSG00000248285 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 2884 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR1A	NM_000524.4 link	c.552C>T	p.Pro184Pro	synonymous_variant	Exon 1 of 1	ENST00000323865.5	NP_000515.2	P08908Q5ZGX3A8K5W4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR1A	ENST00000323865.5 link	c.552C>T	p.Pro184Pro	synonymous_variant	Exon 1 of 1	6	NM_000524.4	ENSP00000316244.4		P08908
ENSG00000248285	ENST00000502882.1 link	n.97-3153C>T		intron_variant	Intron 1 of 1	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

GnomAD2 exomes

AF:

0.0197

AC:

4905

AN:

249262

AF XY:

0.0204

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 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

African (AFR)

AF:

0.0185

AC:

620

AN:

33480

American (AMR)

AF:

0.0214

AC:

955

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

385

AN:

26136

East Asian (EAS)

AF:

0.0314

AC:

1247

AN:

39700

South Asian (SAS)

AF:

0.0317

AC:

2736

AN:

86258

European-Finnish (FIN)

AF:

0.00358

AC:

191

AN:

53350

Middle Eastern (MID)

AF:

0.0205

AC:

118

AN:

5768

European-Non Finnish (NFE)

AF:

0.0172

AC:

19091

AN:

1112010

Other (OTH)

AF:

0.0190

AC:

1149

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

2025

4050

6074

8099

10124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0189

AC:

2884

AN:

152336

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

1405

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0177

AC:

738

AN:

41586

American (AMR)

AF:

0.0287

AC:

440

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3470

East Asian (EAS)

AF:

0.0356

AC:

184

AN:

5164

South Asian (SAS)

AF:

0.0305

AC:

147

AN:

4826

European-Finnish (FIN)

AF:

0.00320

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0167

AC:

1139

AN:

68032

Other (OTH)

AF:

0.0236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

153

307

460

614

767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

(source)

DANN

Benign

0.91

PhyloP100

0.54

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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rs34118353

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over