5-148546000-G-C

Position:

• chr5-148546000-G-C

Variant summary

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

The NM_000870.7(HTR4):​c.353+2668C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,066 control chromosomes in the GnomAD database, including 5,733 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 0.25 (5733 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR4	NM_000870.7	c.353+2668C>G		intron_variant		ENST00000377888.8
LOC107986462	XR_001742935.2	n.442-4085G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR4	ENST00000377888.8	c.353+2668C>G		intron_variant		1	NM_000870.7

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38645 AN: 151948 Hom.: 5732 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.254 AC: 38648 AN: 152066 Hom.: 5733 Cov.: 32 AF XY: 0.251 AC XY: 18645 AN XY: 74320

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.252

Alfa AF: 0.288 Hom.: 846

Bravo AF: 0.250

Asia WGS AF: 0.206 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.58

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: rs1368391; hg19: chr5-147925563; COSMIC: COSV58791848; COSMIC: COSV58791848;