rs7733088

Positions:

• chr5-148476770-G-A
• chr5-148476770-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521530.6(HTR4):​c.1077-25498C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,611,204 control chromosomes in the GnomAD database, including 136,008 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 0.39 (12347 hom., cov: 32)
  • Exomes 𝑓: 0.41 (123661 hom.)
• Consequence: HTR4 ENST00000521530.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112

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]

LOC107986462 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC107986462	XR_001742935.2	n.441+7753G>A		intron_variant, non_coding_transcript_variant
HTR4	NM_001040169.2	c.1077-25498C>T		intron_variant			NP_001035259.1
HTR4	NM_001040172.2	c.1077-25C>T		intron_variant			NP_001035262.2
HTR4	NM_199453.3	c.1077-10845C>T		intron_variant			NP_955525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR4	ENST00000517929.5	c.1077-25C>T		intron_variant		1		ENSP00000435904
HTR4	ENST00000521530.6	c.1077-25498C>T		intron_variant		1		ENSP00000428320	P1
HTR4	ENST00000521735.5	c.1077-10845C>T		intron_variant		1		ENSP00000430979
HTR4	ENST00000522588.5	c.1077-10845C>T		intron_variant, NMD_transcript_variant		1		ENSP00000430874

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59743 AN: 151826 Hom.: 12340 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.373

GnomAD3 exomes AF: 0.441 AC: 108052 AN: 245090 Hom.: 25479 AF XY: 0.432 AC XY: 57575 AN XY: 133232

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.659

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.616

Gnomad SAS exome AF: 0.404

Gnomad FIN exome AF: 0.390

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.407 AC: 593616 AN: 1459260 Hom.: 123661 Cov.: 35 AF XY: 0.406 AC XY: 294861 AN XY: 725984

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.640

Gnomad4 ASJ exome AF: 0.367

Gnomad4 EAS exome AF: 0.558

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.393 AC: 59786 AN: 151944 Hom.: 12347 Cov.: 32 AF XY: 0.397 AC XY: 29438 AN XY: 74238

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.376

Alfa AF: 0.397 Hom.: 21945

Bravo AF: 0.404

Asia WGS AF: 0.517 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7733088; hg19: chr5-147856333; COSMIC: COSV58795812; COSMIC: COSV58795812;