rs10078551

Variant names:

• chr5-148621907-T-C
• rs10078551
• NM_000870.7:c.26+15082A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000870.7(HTR4):​c.26+15082A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,070 control chromosomes in the GnomAD database, including 5,883 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 0.27 (5883 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR4	NM_000870.7	c.26+15082A>G		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.26+15082A>G		intron_variant	Intron 2 of 6	1	NM_000870.7	ENSP00000367120.4

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40372 AN: 151952 Hom.: 5886 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.265 AC: 40366 AN: 152070 Hom.: 5883 Cov.: 32 AF XY: 0.262 AC XY: 19481 AN XY: 74340

African (AFR) AF: 0.148 AC: 6132 AN: 41492

American (AMR) AF: 0.221 AC: 3381 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1055 AN: 5170

South Asian (SAS) AF: 0.283 AC: 1366 AN: 4822

European-Finnish (FIN) AF: 0.318 AC: 3364 AN: 10564

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22890 AN: 67970

Other (OTH) AF: 0.282 AC: 597 AN: 2114

Alfa AF: 0.307 Hom.: 19515

Bravo AF: 0.253

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.66
PhyloP100		1.5
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: rs10078551; hg19: chr5-148001470;