chr5-148608414-C-T

Variant names:

• chr5-148608414-C-T
• rs1011427
• NM_000870.7:c.26+28575G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000870.7(HTR4):​c.26+28575G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 151,918 control chromosomes in the GnomAD database, including 2,577 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 0.15 (2577 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 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.26+28575G>A		intron	N/A	NP_000861.1	A0A2D3FAF9
	HTR4	NM_001040173.2		c.26+28575G>A		intron	N/A	NP_001035263.1	Q13639-8
	HTR4	NM_001286410.1		c.26+28575G>A		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.26+28575G>A		intron	N/A	ENSP00000367120.4	Q13639-1
	HTR4	ENST00000520514.5	TSL:1	c.26+28575G>A		intron	N/A	ENSP00000427913.1	Q13639-9
	HTR4	ENST00000521530.6	TSL:1	c.26+28575G>A		intron	N/A	ENSP00000428320.1	Q13639-2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23352 AN: 151802 Hom.: 2576 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.0684

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0812

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.154 AC: 23365 AN: 151918 Hom.: 2577 Cov.: 32 AF XY: 0.154 AC XY: 11449 AN XY: 74258

African (AFR) AF: 0.302 AC: 12514 AN: 41424

American (AMR) AF: 0.0911 AC: 1390 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1709 AN: 5152

South Asian (SAS) AF: 0.155 AC: 746 AN: 4802

European-Finnish (FIN) AF: 0.0684 AC: 721 AN: 10540

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.0812 AC: 5520 AN: 67956

Other (OTH) AF: 0.142 AC: 300 AN: 2112

Alfa AF: 0.104 Hom.: 946

Bravo AF: 0.162

Asia WGS AF: 0.252 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.63
DANN	Benign	0.52
PhyloP100		-0.23
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: rs1011427; hg19: chr5-147987977;