rs7700268

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.346 AC: 14235 AN: 41186

American (AMR) AF: 0.368 AC: 5603 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3464

East Asian (EAS) AF: 0.565 AC: 2880 AN: 5098

South Asian (SAS) AF: 0.442 AC: 2124 AN: 4808

European-Finnish (FIN) AF: 0.374 AC: 3916 AN: 10468

Middle Eastern (MID) AF: 0.341 AC: 99 AN: 290

European-Non Finnish (NFE) AF: 0.394 AC: 26710 AN: 67842

Other (OTH) AF: 0.400 AC: 840 AN: 2102

Alfa AF: 0.375 Hom.: 1367

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
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7700268; hg19: chr5-148035256;