rs1422636

Positions:

• chr5-148552638-G-A
• chr5-148552638-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.27-2376C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,112 control chromosomes in the GnomAD database, including 50,546 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 0.81 (50546 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR4	NM_000870.7	c.27-2376C>T		intron_variant		ENST00000377888.8	NP_000861.1
LOC107986462	XR_001742935.2	n.708+2287G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8	c.27-2376C>T		intron_variant		1	NM_000870.7	ENSP00000367120

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123452 AN: 151994 Hom.: 50508 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.812 AC: 123549 AN: 152112 Hom.: 50546 Cov.: 32 AF XY: 0.810 AC XY: 60226 AN XY: 74338

Gnomad4 AFR AF: 0.887

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.791

Alfa AF: 0.778 Hom.: 44939

Bravo AF: 0.826

Asia WGS AF: 0.881 AC: 3060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.8
DANN	Benign	0.46

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: rs1422636; hg19: chr5-147932201;