rs10078551

Positions:

• chr5-148621907-T-C

Variant summary

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

The NM_000870.7(HTR4):​c.26+15082A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,070 control chromosomes in the GnomAD database, including 5,883 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 0.27 (5883 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

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=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR4	NM_000870.7	c.26+15082A>G		intron_variant		ENST00000377888.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR4	ENST00000377888.8	c.26+15082A>G		intron_variant		1	NM_000870.7

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40372 AN: 151952 Hom.: 5886 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.265 AC: 40366 AN: 152070 Hom.: 5883 Cov.: 32 AF XY: 0.262 AC XY: 19481 AN XY: 74340

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.282

Alfa AF: 0.319 Hom.: 7683

Bravo AF: 0.253

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.66

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: rs10078551; hg19: chr5-148001470;