5-148662667-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520086.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	ENST00000520086.1	TSL:2	c.156C>A	p.Ile52Ile	synonymous	Exon 2 of 4	ENSP00000429634.1
	HTR4	ENST00000519495.1	TSL:5	n.610C>A		non_coding_transcript_exon	Exon 5 of 7

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

GnomAD2 exomes AF: 0.249 AC: 31992 AN: 128246 AF XY: 0.246

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 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

African (AFR) AF: 0.0711 AC: 1124 AN: 15806

American (AMR) AF: 0.255 AC: 8835 AN: 34694

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 5750 AN: 20016

East Asian (EAS) AF: 0.366 AC: 11737 AN: 32076

South Asian (SAS) AF: 0.224 AC: 14043 AN: 62698

European-Finnish (FIN) AF: 0.216 AC: 7162 AN: 33178

Middle Eastern (MID) AF: 0.231 AC: 942 AN: 4076

European-Non Finnish (NFE) AF: 0.235 AC: 74428 AN: 316844

Other (OTH) AF: 0.233 AC: 7123 AN: 30582

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

African (AFR) AF: 0.0694 AC: 2881 AN: 41530

American (AMR) AF: 0.255 AC: 3898 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 936 AN: 3466

East Asian (EAS) AF: 0.393 AC: 2031 AN: 5164

South Asian (SAS) AF: 0.222 AC: 1067 AN: 4816

European-Finnish (FIN) AF: 0.229 AC: 2418 AN: 10582

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15922 AN: 67980

Other (OTH) AF: 0.227 AC: 480 AN: 2110

Alfa AF: 0.214 Hom.: 731

Bravo AF: 0.195

Asia WGS AF: 0.282 AC: 981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.65
DANN	Benign	0.54
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7720668; hg19: chr5-148042230; COSMIC: COSV107544335;