5-148632176-T-C

Variant names:

• chr5-148632176-T-C
• rs5028114
• NM_000870.7:c.26+4813A>G

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+4813A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,024 control chromosomes in the GnomAD database, including 36,933 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 0.68 (36933 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.912 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+4813A>G		intron	N/A	NP_000861.1
	HTR4	NM_001040173.2		c.26+4813A>G		intron	N/A	NP_001035263.1
	HTR4	NM_001286410.1		c.26+4813A>G		intron	N/A	NP_001273339.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	ENST00000377888.8	TSL:1 MANE Select	c.26+4813A>G		intron	N/A	ENSP00000367120.4
	HTR4	ENST00000520514.5	TSL:1	c.26+4813A>G		intron	N/A	ENSP00000427913.1
	HTR4	ENST00000521530.6	TSL:1	c.26+4813A>G		intron	N/A	ENSP00000428320.1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103260 AN: 151906 Hom.: 36879 Cov.: 32

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.680 AC: 103376 AN: 152024 Hom.: 36933 Cov.: 32 AF XY: 0.677 AC XY: 50260 AN XY: 74294

African (AFR) AF: 0.919 AC: 38181 AN: 41534

American (AMR) AF: 0.613 AC: 9356 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1915 AN: 3464

East Asian (EAS) AF: 0.726 AC: 3754 AN: 5170

South Asian (SAS) AF: 0.679 AC: 3267 AN: 4808

European-Finnish (FIN) AF: 0.556 AC: 5862 AN: 10542

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 38987 AN: 67930

Other (OTH) AF: 0.652 AC: 1376 AN: 2110

Alfa AF: 0.598 Hom.: 14171

Bravo AF: 0.693

Asia WGS AF: 0.731 AC: 2539 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.058
DANN	Benign	0.36
PhyloP100		-0.74
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: rs5028114; hg19: chr5-148011739;