chr5-148467144-A-G

Variant names:

• chr5-148467144-A-G
• rs6889822
• ENST00000521530.6:c.1077-15872T>C

Variant summary

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

The ENST00000521530.6(HTR4):​c.1077-15872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,018 control chromosomes in the GnomAD database, including 9,901 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 0.35 (9901 hom., cov: 32)
• Consequence: HTR4 ENST00000521530.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521530.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	NM_001040169.2		c.1077-15872T>C		intron	N/A	NP_001035259.1
	HTR4	NM_199453.3		c.1077-1219T>C		intron	N/A	NP_955525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR4	ENST00000521530.6	TSL:1	c.1077-15872T>C		intron	N/A	ENSP00000428320.1
	HTR4	ENST00000521735.5	TSL:1	c.1077-1219T>C		intron	N/A	ENSP00000430979.1
	HTR4	ENST00000522588.5	TSL:1	n.1077-1219T>C		intron	N/A	ENSP00000430874.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52580 AN: 151900 Hom.: 9902 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.346 AC: 52588 AN: 152018 Hom.: 9901 Cov.: 32 AF XY: 0.347 AC XY: 25820 AN XY: 74310

African (AFR) AF: 0.208 AC: 8622 AN: 41476

American (AMR) AF: 0.430 AC: 6572 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1212 AN: 3470

East Asian (EAS) AF: 0.618 AC: 3190 AN: 5162

South Asian (SAS) AF: 0.355 AC: 1709 AN: 4818

European-Finnish (FIN) AF: 0.377 AC: 3977 AN: 10550

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26097 AN: 67952

Other (OTH) AF: 0.334 AC: 704 AN: 2108

Alfa AF: 0.353 Hom.: 4456

Bravo AF: 0.351

Asia WGS AF: 0.447 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.66
PhyloP100		0.29
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: rs6889822; hg19: chr5-147846707;