rs4597955

Positions:

• chr5-148467710-G-A
• chr5-148467710-G-C
• chr5-148467710-G-T

Variant summary

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

The NM_001040169.2(HTR4):​c.1077-16438C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,184 control chromosomes in the GnomAD database, including 39,339 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 0.70 (39339 hom., cov: 33)
• Consequence: HTR4 NM_001040169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR4	NM_001040169.2	c.1077-16438C>T		intron_variant			NP_001035259.1
HTR4	NM_199453.3	c.1077-1785C>T		intron_variant			NP_955525.1
LOC107986462	XR_001742935.2	n.344-1210G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000521530.6	c.1077-16438C>T		intron_variant		1		ENSP00000428320.1
HTR4	ENST00000521735.5	c.1077-1785C>T		intron_variant		1		ENSP00000430979.1
HTR4	ENST00000522588.5	n.1077-1785C>T		intron_variant		1		ENSP00000430874.1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106720 AN: 152066 Hom.: 39271 Cov.: 33

Gnomad AFR AF: 0.915

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.702 AC: 106847 AN: 152184 Hom.: 39339 Cov.: 33 AF XY: 0.703 AC XY: 52287 AN XY: 74394

Gnomad4 AFR AF: 0.915

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.656

Alfa AF: 0.599 Hom.: 36607

Bravo AF: 0.722

Asia WGS AF: 0.810 AC: 2813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.0
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4597955; hg19: chr5-147847273;