rs10515616

Variant names:

• chr5-148559399-A-G
• rs10515616
• NM_000870.7:c.27-9137T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-148559399-A-G
• chr5-148559399-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000300418 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HTR4	NM_000870.7	c.27-9137T>C		intron_variant	Intron 2 of 6	ENST00000377888.8	NP_000861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8	c.27-9137T>C		intron_variant	Intron 2 of 6	1	NM_000870.7	ENSP00000367120.4

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

African (AFR) AF: 0.478 AC: 19826 AN: 41438

American (AMR) AF: 0.502 AC: 7666 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1242 AN: 3468

East Asian (EAS) AF: 0.529 AC: 2734 AN: 5172

South Asian (SAS) AF: 0.363 AC: 1750 AN: 4820

European-Finnish (FIN) AF: 0.440 AC: 4644 AN: 10546

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31766 AN: 67956

Other (OTH) AF: 0.456 AC: 963 AN: 2112

Alfa AF: 0.462 Hom.: 2792

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
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10515616; hg19: chr5-147938962;