rs11168048

Variant names:

• chr5-148462790-T-C
• rs11168048
• ENST00000521530.6:c.1077-11518A>G

Variant summary

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

The NM_001040169.2(HTR4):​c.1077-11518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,040 control chromosomes in the GnomAD database, including 12,291 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 0.38 (12291 hom., cov: 32)
• Consequence: HTR4 NM_001040169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 36 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040169.2. 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_001040169.2		c.1077-11518A>G		intron	N/A	NP_001035259.1	Q13639-2
	HTR4	NM_199453.3		c.*15+3060A>G		intron	N/A	NP_955525.1	Q13639-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	ENST00000521530.6	TSL:1	c.1077-11518A>G		intron	N/A	ENSP00000428320.1	Q13639-2
	HTR4	ENST00000521735.5	TSL:1	c.*15+3060A>G		intron	N/A	ENSP00000430979.1	Q13639-5
	HTR4	ENST00000522588.5	TSL:1	n.*16-847A>G		intron	N/A	ENSP00000430874.1	Q13639-5

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58260 AN: 151922 Hom.: 12285 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.383 AC: 58281 AN: 152040 Hom.: 12291 Cov.: 32 AF XY: 0.387 AC XY: 28791 AN XY: 74306

African (AFR) AF: 0.229 AC: 9504 AN: 41484

American (AMR) AF: 0.526 AC: 8024 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1336 AN: 3466

East Asian (EAS) AF: 0.697 AC: 3607 AN: 5176

South Asian (SAS) AF: 0.429 AC: 2072 AN: 4828

European-Finnish (FIN) AF: 0.401 AC: 4235 AN: 10550

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.414 AC: 28165 AN: 67952

Other (OTH) AF: 0.382 AC: 807 AN: 2114

Alfa AF: 0.408 Hom.: 39280

Bravo AF: 0.391

Asia WGS AF: 0.551 AC: 1910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11168048; hg19: chr5-147842353;