5-148448104-A-G

Variant names:

• chr5-148448104-A-G
• rs1984789
• ENST00000521530:c.*3081T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521530(HTR4):​c.*3081T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,066 control chromosomes in the GnomAD database, including 15,769 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 0.42 (15769 hom., cov: 32)
• Consequence: HTR4 ENST00000521530 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 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	ENST00000521530	c.*3081T>C		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000428320.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63441 AN: 151950 Hom.: 15720 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.418 AC: 63544 AN: 152066 Hom.: 15769 Cov.: 32 AF XY: 0.417 AC XY: 30971 AN XY: 74350

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.580

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.387

Alfa AF: 0.350 Hom.: 1331

Bravo AF: 0.434

Asia WGS AF: 0.505 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1984789; hg19: chr5-147827667;