rs34118353

chr5-63961168-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.541

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]

(HGNC:):

ACMG classification

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 GnomAd at 2881 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2881 AN: 152218 Hom.: 53 Cov.: 33

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

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

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

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

Other links and lift over

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