5-148662667-G-T

Variant names:

• chr5-148662667-G-T
• rs7720668
• ENST00000520086.1:c.156C>A

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.Ile52Ile) 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000520086.1	c.156C>A	p.Ile52Ile	synonymous_variant	Exon 2 of 4	2		ENSP00000429634.1
HTR4	ENST00000519495.1	n.610C>A		non_coding_transcript_exon_variant	Exon 5 of 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;