5-148645595-C-T

Position:

• chr5-148645595-C-T

Variant summary

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

The NM_000870.7(HTR4):​c.-48+8467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 152,166 control chromosomes in the GnomAD database, including 55,384 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 0.85 (55381 hom., cov: 31)
  • Exomes 𝑓: 1.0 (3 hom.)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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]

ENSG00000253297 (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 (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR4	NM_000870.7	c.-48+8467G>A		intron_variant		ENST00000377888.8	NP_000861.1
HTR4	NR_104445.2	n.466+8467G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8	c.-48+8467G>A		intron_variant		1	NM_000870.7	ENSP00000367120.4

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129201 AN: 152042 Hom.: 55326 Cov.: 31

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.824

GnomAD4 exome AF: 1.00 AC: 6 AN: 6 Hom.: 3 Cov.: 0 AF XY: 1.00 AC XY: 6 AN XY: 6

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.850 AC: 129311 AN: 152160 Hom.: 55381 Cov.: 31 AF XY: 0.850 AC XY: 63235 AN XY: 74372

Gnomad4 AFR AF: 0.961

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.898

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.800

Gnomad4 OTH AF: 0.827

Alfa AF: 0.800 Hom.: 54771

Bravo AF: 0.853

Asia WGS AF: 0.908 AC: 3154 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	1.5
DANN	Benign	0.49

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: rs7713886; hg19: chr5-148025158;