rs1730208

chr7-155084070-G-A

Variant summary

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

The NM_024012.4(HTR5A):c.742-85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,107,978 control chromosomes in the GnomAD database, including 43,600 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 0.22 (4654 hom., cov: 31)
  • Exomes 𝑓: 0.28 (38946 hom.)
• Consequence: HTR5A NM_024012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

HTR5A (HGNC:5300): (5-hydroxytryptamine receptor 5A) The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects. The gene described in this record is a member of 5-hydroxytryptamine (serotonin) receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to G-proteins. This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR5A	NM_024012.4	c.742-85G>A		intron_variant		ENST00000287907.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR5A	ENST00000287907.3	c.742-85G>A		intron_variant		1	NM_024012.4	P1
HTR5A	ENST00000486819.1	n.98-85G>A		intron_variant, non_coding_transcript_variant		1
HTR5A	ENST00000649716.1	c.*211-85G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33702 AN: 151818 Hom.: 4645 Cov.: 31

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.278 AC: 265878 AN: 956042 Hom.: 38946 AF XY: 0.280 AC XY: 133586 AN XY: 477522

Gnomad4 AFR exome AF: 0.0450

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.173

Gnomad4 SAS exome AF: 0.304

Gnomad4 FIN exome AF: 0.380

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.222 AC: 33716 AN: 151936 Hom.: 4654 Cov.: 31 AF XY: 0.225 AC XY: 16729 AN XY: 74250

Gnomad4 AFR AF: 0.0539

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.247

Alfa AF: 0.258 Hom.: 982

Bravo AF: 0.202

Asia WGS AF: 0.299 AC: 1037 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	0.30
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs1730208; hg19: chr7-154875780; COSMIC: COSV55280155;