chr5-148523525-G-T

Variant names:

• chr5-148523525-G-T
• rs2277049
• NM_000870.7:c.354-179C>A

Variant summary

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

The NM_000870.7(HTR4):​c.354-179C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 151,344 control chromosomes in the GnomAD database, including 3,729 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 0.17 (3729 hom., cov: 31)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392
• 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]

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 (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR4	NM_000870.7	c.354-179C>A		intron_variant	Intron 4 of 6	ENST00000377888.8	NP_000861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8	c.354-179C>A		intron_variant	Intron 4 of 6	1	NM_000870.7	ENSP00000367120.4

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25649 AN: 151228 Hom.: 3724 Cov.: 31

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0683

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0587

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.170 AC: 25689 AN: 151344 Hom.: 3729 Cov.: 31 AF XY: 0.169 AC XY: 12524 AN XY: 73952

African (AFR) AF: 0.388 AC: 15916 AN: 41012

American (AMR) AF: 0.170 AC: 2583 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3468

East Asian (EAS) AF: 0.282 AC: 1444 AN: 5120

South Asian (SAS) AF: 0.105 AC: 502 AN: 4800

European-Finnish (FIN) AF: 0.0683 AC: 719 AN: 10526

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0587 AC: 3985 AN: 67908

Other (OTH) AF: 0.148 AC: 310 AN: 2098

Alfa AF: 0.0866 Hom.: 563

Bravo AF: 0.186

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.44
PhyloP100		-0.39
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: rs2277049; hg19: chr5-147903088;