5-148662667-G-T

Position:

• chr5-148662667-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000520086.1(HTR4):​c.156C>A​(p.Ile52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 702,110 control chromosomes in the GnomAD database, including 20,180 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 0.20 (3595 hom., cov: 33)
  • Exomes 𝑓: 0.24 (16585 hom.)
• Consequence: HTR4 ENST00000520086.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-0.458 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000520086.1	c.156C>A	p.Ile52=	synonymous_variant	2/4	2		ENSP00000429634
HTR4	ENST00000519495.1	n.610C>A		non_coding_transcript_exon_variant	5/7	5

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30145 AN: 152022 Hom.: 3599 Cov.: 33

Gnomad AFR AF: 0.0696

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.229

GnomAD3 exomes AF: 0.249 AC: 31992 AN: 128246 Hom.: 4378 AF XY: 0.246 AC XY: 17303 AN XY: 70234

Gnomad AFR exome AF: 0.0634

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.416

Gnomad SAS exome AF: 0.224

Gnomad FIN exome AF: 0.215

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.243

GnomAD4 exome AF: 0.238 AC: 131144 AN: 549970 Hom.: 16585 Cov.: 0 AF XY: 0.238 AC XY: 70890 AN XY: 297714

Gnomad4 AFR exome AF: 0.0711

Gnomad4 AMR exome AF: 0.255

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.366

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.198 AC: 30123 AN: 152140 Hom.: 3595 Cov.: 33 AF XY: 0.200 AC XY: 14908 AN XY: 74390

Gnomad4 AFR AF: 0.0694

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.227

Alfa AF: 0.218 Hom.: 730

Bravo AF: 0.195

Asia WGS AF: 0.282 AC: 981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.65
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7720668; hg19: chr5-148042230;