rs888961

Positions:

• chr5-148659334-C-A
• chr5-148659334-C-G

Variant summary

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

The ENST00000520086.1(HTR4):​c.216+3273G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,190 control chromosomes in the GnomAD database, including 3,415 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 0.19 (3415 hom., cov: 32)
• Consequence: HTR4 ENST00000520086.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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=-0.83).
• 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	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR4	ENST00000520086.1	c.216+3273G>T		intron_variant		2
HTR4	ENST00000519495.1	n.670+3273G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29436 AN: 152072 Hom.: 3417 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.193 AC: 29416 AN: 152190 Hom.: 3415 Cov.: 32 AF XY: 0.196 AC XY: 14576 AN XY: 74418

Gnomad4 AFR AF: 0.0684

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.223

Alfa AF: 0.199 Hom.: 1589

Bravo AF: 0.190

Asia WGS AF: 0.279 AC: 971 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	4.2
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs888961; hg19: chr5-148038897;