rs888961

Variant names:

• chr5-148659334-C-A
• rs888961
• ENST00000520086.1:c.216+3273G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-148659334-C-A
• chr5-148659334-C-G

Variant summary

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

The ENST00000520086.1(HTR4):​c.216+3273G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,190 control chromosomes in the GnomAD database, including 3,415 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 0.19 (3415 hom., cov: 32)
• Consequence: HTR4 ENST00000520086.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520086.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	ENST00000520086.1	TSL:2	c.216+3273G>T		intron	N/A	ENSP00000429634.1	E5RHV8
	HTR4	ENST00000519495.1	TSL:5	n.670+3273G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29436 AN: 152072 Hom.: 3417 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.193 AC: 29416 AN: 152190 Hom.: 3415 Cov.: 32 AF XY: 0.196 AC XY: 14576 AN XY: 74418

African (AFR) AF: 0.0684 AC: 2841 AN: 41526

American (AMR) AF: 0.247 AC: 3774 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3470

East Asian (EAS) AF: 0.393 AC: 2034 AN: 5176

South Asian (SAS) AF: 0.211 AC: 1016 AN: 4814

European-Finnish (FIN) AF: 0.226 AC: 2403 AN: 10610

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15513 AN: 67994

Other (OTH) AF: 0.223 AC: 469 AN: 2106

Alfa AF: 0.201 Hom.: 1789

Bravo AF: 0.190

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.77
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs888961;

hg19: chr5-148038897;