chr5-148573982-G-A

Variant names:

• chr5-148573982-G-A
• rs7715569
• NM_000870.7:c.27-23720C>T

Variant summary

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

The NM_000870.7(HTR4):​c.27-23720C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 151,926 control chromosomes in the GnomAD database, including 5,106 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 0.24 (5106 hom., cov: 32)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 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.27-23720C>T		intron	N/A	NP_000861.1	A0A2D3FAF9
	HTR4	NM_001040173.2		c.27-23720C>T		intron	N/A	NP_001035263.1	Q13639-8
	HTR4	NM_001286410.1		c.27-23720C>T		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.27-23720C>T		intron	N/A	ENSP00000367120.4	Q13639-1
	HTR4	ENST00000520514.5	TSL:1	c.27-23720C>T		intron	N/A	ENSP00000427913.1	Q13639-9
	HTR4	ENST00000521530.6	TSL:1	c.27-23720C>T		intron	N/A	ENSP00000428320.1	Q13639-2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35731 AN: 151808 Hom.: 5103 Cov.: 32

Gnomad AFR AF: 0.0767

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.235 AC: 35731 AN: 151926 Hom.: 5106 Cov.: 32 AF XY: 0.231 AC XY: 17193 AN XY: 74270

African (AFR) AF: 0.0765 AC: 3174 AN: 41486

American (AMR) AF: 0.264 AC: 4018 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3468

East Asian (EAS) AF: 0.243 AC: 1252 AN: 5144

South Asian (SAS) AF: 0.214 AC: 1032 AN: 4822

European-Finnish (FIN) AF: 0.253 AC: 2673 AN: 10562

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22017 AN: 67890

Other (OTH) AF: 0.234 AC: 493 AN: 2108

Alfa AF: 0.272 Hom.: 784

Bravo AF: 0.232

Asia WGS AF: 0.209 AC: 727 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	3.5
DANN	Benign	0.45
PhyloP100		1.2
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: rs7715569; hg19: chr5-147953545; COSMIC: COSV58791971;