rs17706683

chr5-148544692-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000870.7(HTR4):c.353+3976A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 152,284 control chromosomes in the GnomAD database, including 133 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 0.034 (133 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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=-0.73).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0336 (5118/152284) while in subpopulation NFE AF= 0.0412 (2800/68028). AF 95% confidence interval is 0.0399. There are 133 homozygotes in gnomad4. There are 2694 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 133 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR4	NM_000870.7	c.353+3976A>T		intron_variant		ENST00000377888.8
LOC107986462	XR_001742935.2	n.442-5393T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR4	ENST00000377888.8	c.353+3976A>T		intron_variant		1	NM_000870.7

Frequencies

GnomAD3 genomes AF: 0.0336 AC: 5120 AN: 152166 Hom.: 133 Cov.: 32

Gnomad AFR AF: 0.00750

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0400

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00829

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0412

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0336 AC: 5118 AN: 152284 Hom.: 133 Cov.: 32 AF XY: 0.0362 AC XY: 2694 AN XY: 74458

Gnomad4 AFR AF: 0.00748

Gnomad4 AMR AF: 0.0399

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00830

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0412

Gnomad4 OTH AF: 0.0425

Alfa AF: 0.0337 Hom.: 17

Bravo AF: 0.0287

Asia WGS AF: 0.00924 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	8.0
Dann	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs17706683; hg19: chr5-147924255;