rs7700268

chr5-148655693-G-A

Variant summary

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

The ENST00000520086.1(HTR4):c.216+6914C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,370 control chromosomes in the GnomAD database, including 11,440 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 0.39 (11440 hom., cov: 29)
• Consequence: HTR4 ENST00000520086.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 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+6914C>T		intron_variant		2
HTR4	ENST00000519495.1	n.670+6914C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58293 AN: 151254 Hom.: 11432 Cov.: 29

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.385 AC: 58319 AN: 151370 Hom.: 11440 Cov.: 29 AF XY: 0.386 AC XY: 28510 AN XY: 73950

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.400

Alfa AF: 0.375 Hom.: 1315

Bravo AF: 0.382

Asia WGS AF: 0.528 AC: 1835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	6.5
Dann	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7700268; hg19: chr5-148035256;