rs13166761

Variant names:

• chr5-148567725-C-T
• rs13166761
• NM_000870.7:c.27-17463G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000870.7(HTR4):​c.27-17463G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 151,968 control chromosomes in the GnomAD database, including 5,094 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 0.23 (5094 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR4	NM_000870.7	c.27-17463G>A		intron_variant	Intron 2 of 6	ENST00000377888.8	NP_000861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8	c.27-17463G>A		intron_variant	Intron 2 of 6	1	NM_000870.7	ENSP00000367120.4

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35709 AN: 151850 Hom.: 5090 Cov.: 32

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.233

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.235 AC: 35710 AN: 151968 Hom.: 5094 Cov.: 32 AF XY: 0.231 AC XY: 17180 AN XY: 74252

Gnomad4 AFR AF: 0.0764

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.233

Alfa AF: 0.272 Hom.: 790

Bravo AF: 0.232

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.76

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: rs13166761; hg19: chr5-147947288; COSMIC: COSV58791948;