rs34118353

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

2

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]

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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
HTR1ANM_000524.4 linkuse as main transcriptc.552C>T p.Pro184= synonymous_variant 1/1 ENST00000323865.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HTR1AENST00000323865.5 linkuse as main transcriptc.552C>T p.Pro184= synonymous_variant 1/1 NM_000524.4 P1
ENST00000502882.1 linkuse as main transcriptn.97-3153C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0189
AC:
2881
AN:
152218
Hom.:
53
Cov.:
33
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.:
67
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.:
31
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.:
52
Cov.:
33
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.:
18
Bravo
AF:
0.0219
Asia WGS
AF:
0.0230
AC:
81
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.

Other links and lift over

dbSNP: rs34118353; hg19: chr5-63256995; COSMIC: COSV60499847; COSMIC: COSV60499847; API