rs10061244

Variant names:

• chr5-148478585-A-G
• rs10061244
• ENST00000521530.6:c.1077-27313T>C

Variant summary

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

The NM_001040169.2(HTR4):​c.1077-27313T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,134 control chromosomes in the GnomAD database, including 1,767 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 0.12 (1767 hom., cov: 32)
• Consequence: HTR4 NM_001040169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 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.1077-27313T>C		intron	N/A	NP_001035259.1	Q13639-2
	HTR4	NM_199453.3		c.1077-12660T>C		intron	N/A	NP_955525.1	Q13639-5
	HTR4	NM_001040172.2		c.1077-1840T>C		intron	N/A	NP_001035262.2	Q13639-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	ENST00000521530.6	TSL:1	c.1077-27313T>C		intron	N/A	ENSP00000428320.1	Q13639-2
	HTR4	ENST00000521735.5	TSL:1	c.1077-12660T>C		intron	N/A	ENSP00000430979.1	Q13639-5
	HTR4	ENST00000517929.5	TSL:1	c.1077-1840T>C		intron	N/A	ENSP00000435904.1	Q13639-3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18521 AN: 152016 Hom.: 1766 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0616

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.122 AC: 18549 AN: 152134 Hom.: 1767 Cov.: 32 AF XY: 0.122 AC XY: 9067 AN XY: 74394

African (AFR) AF: 0.260 AC: 10772 AN: 41472

American (AMR) AF: 0.0524 AC: 801 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3468

East Asian (EAS) AF: 0.166 AC: 859 AN: 5162

South Asian (SAS) AF: 0.0708 AC: 342 AN: 4830

European-Finnish (FIN) AF: 0.117 AC: 1237 AN: 10604

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0616 AC: 4189 AN: 68004

Other (OTH) AF: 0.100 AC: 212 AN: 2112

Alfa AF: 0.150 Hom.: 963

Bravo AF: 0.123

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.56
PhyloP100		0.0050
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: rs10061244; hg19: chr5-147858148;