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. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000520086.1	c.216+3273G>T		intron_variant	Intron 2 of 3	2		ENSP00000429634.1
HTR4	ENST00000519495.1	n.670+3273G>T		intron_variant	Intron 5 of 6	5

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

Gnomad4 AFR AF: 0.0684

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.223

Alfa AF: 0.199 Hom.: 1589

Bravo AF: 0.190

Asia WGS AF: 0.279 AC: 971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs888961; hg19: chr5-148038897;