rs3734119

Positions:

• chr5-148510060-A-G
• chr5-148510060-A-T

Variant summary

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

The NM_000870.7(HTR4):​c.508-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0757 in 1,400,284 control chromosomes in the GnomAD database, including 9,018 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 0.15 (3322 hom., cov: 31)
  • Exomes 𝑓: 0.066 (5696 hom.)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.610

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]

LOC107986462 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR4	NM_000870.7	c.508-36T>C		intron_variant		ENST00000377888.8	NP_000861.1
LOC107986462	XR_001742935.2	n.442-40025A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8	c.508-36T>C		intron_variant		1	NM_000870.7	ENSP00000367120

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23493 AN: 151686 Hom.: 3321 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.0769

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.126

GnomAD3 exomes AF: 0.122 AC: 20658 AN: 169514 Hom.: 2162 AF XY: 0.111 AC XY: 9963 AN XY: 90120

Gnomad AFR exome AF: 0.379

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.0466

Gnomad EAS exome AF: 0.306

Gnomad SAS exome AF: 0.0820

Gnomad FIN exome AF: 0.0719

Gnomad NFE exome AF: 0.0499

Gnomad OTH exome AF: 0.0903

GnomAD4 exome AF: 0.0660 AC: 82419 AN: 1248480 Hom.: 5696 Cov.: 16 AF XY: 0.0646 AC XY: 40072 AN XY: 620762

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.0407

Gnomad4 EAS exome AF: 0.287

Gnomad4 SAS exome AF: 0.0733

Gnomad4 FIN exome AF: 0.0706

Gnomad4 NFE exome AF: 0.0431

Gnomad4 OTH exome AF: 0.0837

GnomAD4 genome AF: 0.155 AC: 23516 AN: 151804 Hom.: 3322 Cov.: 31 AF XY: 0.155 AC XY: 11495 AN XY: 74204

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.0374

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.0765

Gnomad4 FIN AF: 0.0644

Gnomad4 NFE AF: 0.0445

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0882 Hom.: 260

Bravo AF: 0.171

Asia WGS AF: 0.162 AC: 561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3734119; hg19: chr5-147889623; COSMIC: COSV58790879;