rs1972644

Positions:

• chr5-148639985-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.-47-2924G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,848 control chromosomes in the GnomAD database, including 13,814 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 0.42 (13814 hom., cov: 31)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR4	NM_000870.7	c.-47-2924G>A		intron_variant		ENST00000377888.8
HTR4	NR_104445.2	n.467-2924G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR4	ENST00000377888.8	c.-47-2924G>A		intron_variant		1	NM_000870.7

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64259 AN: 151730 Hom.: 13806 Cov.: 31

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.423 AC: 64290 AN: 151848 Hom.: 13814 Cov.: 31 AF XY: 0.423 AC XY: 31421 AN XY: 74210

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.433

Alfa AF: 0.414 Hom.: 6300

Bravo AF: 0.424

Asia WGS AF: 0.490 AC: 1703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.99
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1972644; hg19: chr5-148019548;