chr5-148448104-A-G

Position:

• chr5-148448104-A-G

Variant summary

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

The ENST00000521530.6(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 ENST00000521530.6 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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000521530.6	c.*3081T>C		3_prime_UTR_variant	7/7	1		ENSP00000428320	P1

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;