rs7725785

Variant names:

• chr5-148523140-C-A
• rs7725785
• NM_000870.7:c.507+53G>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.507+53G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0892 in 1,453,676 control chromosomes in the GnomAD database, including 11,069 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 (3830 hom., cov: 32)
  • Exomes 𝑓: 0.080 (7239 hom.)
• Consequence: HTR4 NM_000870.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR4	NM_000870.7	c.507+53G>T		intron_variant	Intron 5 of 6	ENST00000377888.8	NP_000861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000377888.8	c.507+53G>T		intron_variant	Intron 5 of 6	1	NM_000870.7	ENSP00000367120.4

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25961 AN: 151866 Hom.: 3825 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0462

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.0796 AC: 103620 AN: 1301692 Hom.: 7239 AF XY: 0.0788 AC XY: 51543 AN XY: 654060

African (AFR) AF: 0.393 AC: 11130 AN: 28348

American (AMR) AF: 0.193 AC: 6896 AN: 35796

Ashkenazi Jewish (ASJ) AF: 0.0498 AC: 1214 AN: 24374

East Asian (EAS) AF: 0.287 AC: 10688 AN: 37234

South Asian (SAS) AF: 0.103 AC: 7862 AN: 76104

European-Finnish (FIN) AF: 0.0730 AC: 3869 AN: 53010

Middle Eastern (MID) AF: 0.0899 AC: 488 AN: 5430

European-Non Finnish (NFE) AF: 0.0568 AC: 56081 AN: 986684

Other (OTH) AF: 0.0986 AC: 5392 AN: 54712

GnomAD4 genome AF: 0.171 AC: 26001 AN: 151984 Hom.: 3830 Cov.: 32 AF XY: 0.170 AC XY: 12655 AN XY: 74280

African (AFR) AF: 0.391 AC: 16195 AN: 41422

American (AMR) AF: 0.170 AC: 2594 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0462 AC: 160 AN: 3462

East Asian (EAS) AF: 0.282 AC: 1456 AN: 5160

South Asian (SAS) AF: 0.105 AC: 504 AN: 4806

European-Finnish (FIN) AF: 0.0682 AC: 721 AN: 10576

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

European-Non Finnish (NFE) AF: 0.0586 AC: 3986 AN: 67984

Other (OTH) AF: 0.150 AC: 315 AN: 2104

Alfa AF: 0.0922 Hom.: 5442

Bravo AF: 0.187

Asia WGS AF: 0.184 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		-0.032
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: rs7725785; hg19: chr5-147902703; COSMIC: COSV58797037;