5-148608414-C-T

Position:

• chr5-148608414-C-T

Variant summary

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

The NM_000870.7(HTR4):​c.26+28575G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 151,918 control chromosomes in the GnomAD database, including 2,577 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 0.15 (2577 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR4	NM_000870.7	c.26+28575G>A		intron_variant		ENST00000377888.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR4	ENST00000377888.8	c.26+28575G>A		intron_variant		1	NM_000870.7

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23352 AN: 151802 Hom.: 2576 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0684

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0812

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.154 AC: 23365 AN: 151918 Hom.: 2577 Cov.: 32 AF XY: 0.154 AC XY: 11449 AN XY: 74258

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.0911

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0684

Gnomad4 NFE AF: 0.0812

Gnomad4 OTH AF: 0.142

Alfa AF: 0.102 Hom.: 780

Bravo AF: 0.162

Asia WGS AF: 0.252 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.63
DANN	Benign	0.52

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: rs1011427; hg19: chr5-147987977;