rs7700268

Variant names:

• chr5-148655693-G-A
• rs7700268
• ENST00000520086.1:c.216+6914C>T

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000520086.1	c.216+6914C>T		intron_variant	Intron 2 of 3	2		ENSP00000429634.1
HTR4	ENST00000519495.1	n.670+6914C>T		intron_variant	Intron 5 of 6	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;