chr5-148658742-T-C

Variant names:

• chr5-148658742-T-C
• rs1862345
• ENST00000520086.1:c.216+3865A>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+3865A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,078 control chromosomes in the GnomAD database, including 11,543 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 0.39 (11543 hom., cov: 32)
• Consequence: HTR4 ENST00000520086.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 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+3865A>G		intron	N/A	ENSP00000429634.1	E5RHV8
	HTR4	ENST00000519495.1	TSL:5	n.670+3865A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58615 AN: 151960 Hom.: 11535 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.386 AC: 58640 AN: 152078 Hom.: 11543 Cov.: 32 AF XY: 0.386 AC XY: 28666 AN XY: 74332

African (AFR) AF: 0.346 AC: 14340 AN: 41488

American (AMR) AF: 0.368 AC: 5628 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1425 AN: 3472

East Asian (EAS) AF: 0.568 AC: 2927 AN: 5152

South Asian (SAS) AF: 0.442 AC: 2131 AN: 4826

European-Finnish (FIN) AF: 0.373 AC: 3941 AN: 10564

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26797 AN: 67978

Other (OTH) AF: 0.401 AC: 847 AN: 2112

Alfa AF: 0.286 Hom.: 998

Bravo AF: 0.382

Asia WGS AF: 0.529 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.6
DANN	Benign	0.68
PhyloP100		0.38
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: rs1862345;

hg19: chr5-148038305;