rs3823534

Positions:

• chr7-155070478-A-G

Variant summary

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

The NM_024012.4(HTR5A):​c.-422A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 394,018 control chromosomes in the GnomAD database, including 18,097 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 0.32 (8104 hom., cov: 32)
  • Exomes 𝑓: 0.28 (9993 hom.)
• Consequence: HTR5A NM_024012.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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]

HTR5A-AS1 (HGNC:48956): (HTR5A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR5A	NM_024012.4	c.-422A>G		5_prime_UTR_variant	1/2	ENST00000287907.3
HTR5A-AS1	NR_038945.1	n.524+556T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR5A	ENST00000287907.3	c.-422A>G		5_prime_UTR_variant	1/2	1	NM_024012.4	P1
HTR5A-AS1	ENST00000671665.1	n.1417+556T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48113 AN: 151922 Hom.: 8076 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.298

GnomAD3 exomes AF: 0.296 AC: 21828 AN: 73852 Hom.: 3428 AF XY: 0.295 AC XY: 11889 AN XY: 40286

Gnomad AFR exome AF: 0.434

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.280

Gnomad EAS exome AF: 0.355

Gnomad SAS exome AF: 0.337

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.295

GnomAD4 exome AF: 0.277 AC: 67109 AN: 241978 Hom.: 9993 Cov.: 0 AF XY: 0.280 AC XY: 38345 AN XY: 136902

Gnomad4 AFR exome AF: 0.431

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.255

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.317 AC: 48196 AN: 152040 Hom.: 8104 Cov.: 32 AF XY: 0.318 AC XY: 23621 AN XY: 74338

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.304

Alfa AF: 0.304 Hom.: 1464

Bravo AF: 0.319

Asia WGS AF: 0.378 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.83

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: rs3823534; hg19: chr7-154862188; COSMIC: COSV55281614; COSMIC: COSV55281614;