rs3734967

chr7-155070798-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.-102A>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 0.279 in 1,236,192 control chromosomes in the GnomAD database, including 51,204 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 0.23 (4960 hom., cov: 33)
  • Exomes 𝑓: 0.29 (46244 hom.)
• Consequence: HTR5A NM_024012.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545

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=-0.63).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR5A	NM_024012.4	c.-102A>G		5_prime_UTR_variant	1/2	ENST00000287907.3
HTR5A-AS1	NR_038945.1	n.524+236T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR5A	ENST00000287907.3	c.-102A>G		5_prime_UTR_variant	1/2	1	NM_024012.4	P1
HTR5A-AS1	ENST00000671665.1	n.1417+236T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34997 AN: 152046 Hom.: 4950 Cov.: 33

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.238

GnomAD4 exome AF: 0.285 AC: 309343 AN: 1084028 Hom.: 46244 Cov.: 15 AF XY: 0.288 AC XY: 155924 AN XY: 541340

Gnomad4 AFR exome AF: 0.0578

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.335

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.230 AC: 35017 AN: 152164 Hom.: 4960 Cov.: 33 AF XY: 0.234 AC XY: 17416 AN XY: 74378

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.244

Alfa AF: 0.243 Hom.: 800

Bravo AF: 0.209

Asia WGS AF: 0.327 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	12
Dann	Benign	0.84

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: rs3734967; hg19: chr7-154862508; COSMIC: COSV55281626; COSMIC: COSV55281626;