rs10515616

chr5-148559399-A-Gchr5-148559399-A-T

Variant summary

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

The NM_000870.7(HTR4):c.27-9137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,982 control chromosomes in the GnomAD database, including 16,797 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 0.47 (16797 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416

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]

LOC107986462 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR4	NM_000870.7	c.27-9137T>C		intron_variant		ENST00000377888.8
LOC107986462	XR_001742935.2	n.709-176A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR4	ENST00000377888.8	c.27-9137T>C		intron_variant		1	NM_000870.7

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71098 AN: 151864 Hom.: 16785 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.468 AC: 71144 AN: 151982 Hom.: 16797 Cov.: 32 AF XY: 0.464 AC XY: 34494 AN XY: 74262

Gnomad4 AFR AF: 0.478

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.456

Alfa AF: 0.461 Hom.: 2700

Bravo AF: 0.476

Asia WGS AF: 0.443 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.77
Dann	Benign	0.45

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: rs10515616; hg19: chr5-147938962;