5-148552638-G-A

Variant names:

• chr5-148552638-G-A
• rs1422636
• NM_000870.7:c.27-2376C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000870.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	NM_000870.7	MANE Select	c.27-2376C>T		intron	N/A	NP_000861.1	A0A2D3FAF9
	HTR4	NM_001040173.2		c.27-2376C>T		intron	N/A	NP_001035263.1	Q13639-8
	HTR4	NM_001286410.1		c.27-2376C>T		intron	N/A	NP_001273339.1	Q13639-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	ENST00000377888.8	TSL:1 MANE Select	c.27-2376C>T		intron	N/A	ENSP00000367120.4	Q13639-1
	HTR4	ENST00000520514.5	TSL:1	c.27-2376C>T		intron	N/A	ENSP00000427913.1	Q13639-9
	HTR4	ENST00000521530.6	TSL:1	c.27-2376C>T		intron	N/A	ENSP00000428320.1	Q13639-2

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

African (AFR) AF: 0.887 AC: 36840 AN: 41528

American (AMR) AF: 0.833 AC: 12722 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2593 AN: 3470

East Asian (EAS) AF: 0.940 AC: 4868 AN: 5176

South Asian (SAS) AF: 0.875 AC: 4211 AN: 4812

European-Finnish (FIN) AF: 0.689 AC: 7274 AN: 10554

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.771 AC: 52421 AN: 67982

Other (OTH) AF: 0.791 AC: 1670 AN: 2112

Alfa AF: 0.790 Hom.: 123467

Bravo AF: 0.826

Asia WGS AF: 0.881 AC: 3060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.8
DANN	Benign	0.46
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1422636; hg19: chr5-147932201;