rs17706683

Variant names:

• chr5-148544692-T-A
• rs17706683
• NM_000870.7:c.353+3976A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000377888.8(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 ENST00000377888.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 0 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]

ENSG00000300418 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 133 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377888.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	NM_000870.7	MANE Select	c.353+3976A>T		intron	N/A	NP_000861.1
	HTR4	NM_001040173.2		c.353+3976A>T		intron	N/A	NP_001035263.1
	HTR4	NM_001286410.1		c.353+3976A>T		intron	N/A	NP_001273339.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	ENST00000377888.8	TSL:1 MANE Select	c.353+3976A>T		intron	N/A	ENSP00000367120.4
	HTR4	ENST00000520514.5	TSL:1	c.353+3976A>T		intron	N/A	ENSP00000427913.1
	HTR4	ENST00000521530.6	TSL:1	c.353+3976A>T		intron	N/A	ENSP00000428320.1

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

African (AFR) AF: 0.00748 AC: 311 AN: 41568

American (AMR) AF: 0.0399 AC: 611 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.00830 AC: 40 AN: 4822

European-Finnish (FIN) AF: 0.101 AC: 1076 AN: 10602

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0412 AC: 2800 AN: 68028

Other (OTH) AF: 0.0425 AC: 90 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.0
DANN	Benign	0.88
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17706683; hg19: chr5-147924255;