5-148587111-A-G

Position:

• chr5-148587111-A-G

Variant summary

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

The NM_000870.7(HTR4):​c.27-36849T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,818 control chromosomes in the GnomAD database, including 24,533 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 0.56 (24533 hom., cov: 31)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

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]

HTR4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR4	NM_000870.7	c.27-36849T>C		intron_variant		ENST00000377888.8	NP_000861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8	c.27-36849T>C		intron_variant		1	NM_000870.7	ENSP00000367120.4

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84743 AN: 151698 Hom.: 24494 Cov.: 31

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.559 AC: 84843 AN: 151818 Hom.: 24533 Cov.: 31 AF XY: 0.556 AC XY: 41227 AN XY: 74168

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.545

Alfa AF: 0.509 Hom.: 4090

Bravo AF: 0.569

Asia WGS AF: 0.525 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.41

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: rs888957; hg19: chr5-147966674;