rs1833710

Variant names:

• chr5-148588183-A-G
• rs1833710
• NM_000870.7:c.27-37921T>C

Variant summary

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

The NM_000870.7(HTR4):​c.27-37921T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,210 control chromosomes in the GnomAD database, including 2,836 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 0.18 (2836 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR4	NM_000870.7	c.27-37921T>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.27-37921T>C		intron_variant	Intron 2 of 6	1	NM_000870.7	ENSP00000367120.4

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27438 AN: 152094 Hom.: 2825 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.0964

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.181 AC: 27498 AN: 152210 Hom.: 2836 Cov.: 32 AF XY: 0.182 AC XY: 13513 AN XY: 74426

African (AFR) AF: 0.252 AC: 10459 AN: 41512

American (AMR) AF: 0.248 AC: 3798 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0964 AC: 334 AN: 3466

East Asian (EAS) AF: 0.178 AC: 922 AN: 5180

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4822

European-Finnish (FIN) AF: 0.152 AC: 1608 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8930 AN: 68008

Other (OTH) AF: 0.166 AC: 351 AN: 2114

Alfa AF: 0.139 Hom.: 2462

Bravo AF: 0.189

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.39
PhyloP100		0.011
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: rs1833710; hg19: chr5-147967746;