11-113977551-A-T

Variant summary

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

The NM_000869.6(HTR3A):c.68-220A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 1,548,166 control chromosomes in the GnomAD database, including 340,475 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 0.57 (26272 hom., cov: 32)
  • Exomes 𝑓: 0.67 (314203 hom.)
• Consequence: HTR3A NM_000869.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.743

Genes affected

HTR3A (HGNC:5297): (5-hydroxytryptamine receptor 3A) The product of this gene belongs to the ligand-gated ion channel receptor superfamily. This gene encodes subunit A of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor causes fast, depolarizing responses in neurons after activation. It appears that the heteromeric combination of A and B subunits is necessary to provide the full functional features of this receptor, since either subunit alone results in receptors with very low conductance and response amplitude. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR3A	NM_000869.6	c.68-220A>T		intron_variant		ENST00000504030.7
HTR3A	NM_001161772.3	c.-4A>T		5_prime_UTR_variant	1/9
HTR3A	NM_213621.4	c.68-220A>T		intron_variant
HTR3A	NR_046363.2	n.286-220A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3A	ENST00000504030.7	c.68-220A>T		intron_variant		1	NM_000869.6	P1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86256 AN: 151902 Hom.: 26274 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.595

GnomAD3 exomes AF: 0.626 AC: 96807 AN: 154570 Hom.: 31082 AF XY: 0.639 AC XY: 52356 AN XY: 81898

Gnomad AFR exome AF: 0.324

Gnomad AMR exome AF: 0.518

Gnomad ASJ exome AF: 0.693

Gnomad EAS exome AF: 0.636

Gnomad SAS exome AF: 0.695

Gnomad FIN exome AF: 0.605

Gnomad NFE exome AF: 0.676

Gnomad OTH exome AF: 0.663

GnomAD4 exome AF: 0.667 AC: 931869 AN: 1396146 Hom.: 314203 Cov.: 34 AF XY: 0.670 AC XY: 461511 AN XY: 688788

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.536

Gnomad4 ASJ exome AF: 0.690

Gnomad4 EAS exome AF: 0.690

Gnomad4 SAS exome AF: 0.695

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.649

GnomAD4 genome AF: 0.567 AC: 86264 AN: 152020 Hom.: 26272 Cov.: 32 AF XY: 0.567 AC XY: 42161 AN XY: 74300

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.593

Alfa AF: 0.630 Hom.: 8397

Bravo AF: 0.554

Asia WGS AF: 0.645 AC: 2243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.45
Dann	Benign	0.36

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: rs1985242; hg19: chr11-113848273;