rs2068190

Positions:

• chr5-148627450-G-A
• chr5-148627450-G-C
• chr5-148627450-G-T

Variant summary

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

The NM_000870.7(HTR4):​c.26+9539C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 152,034 control chromosomes in the GnomAD database, including 18,233 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 0.48 (18233 hom., cov: 33)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470

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]

HTR4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR4	NM_000870.7	c.26+9539C>T		intron_variant		ENST00000377888.8	NP_000861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8	c.26+9539C>T		intron_variant		1	NM_000870.7	ENSP00000367120.4

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73374 AN: 151916 Hom.: 18211 Cov.: 33

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.483 AC: 73444 AN: 152034 Hom.: 18233 Cov.: 33 AF XY: 0.482 AC XY: 35836 AN XY: 74324

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.481

Alfa AF: 0.445 Hom.: 31357

Bravo AF: 0.487

Asia WGS AF: 0.632 AC: 2194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.63

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: rs2068190; hg19: chr5-148007013;