11-113977551-A-T

Variant names:

• chr11-113977551-A-T
• rs1985242
• NM_000869.6:c.68-220A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161772.3(HTR3A):​c.-4A>T variant causes a 5 prime UTR premature start codon gain 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_001161772.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.743
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161772.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	NM_000869.6	MANE Select	c.68-220A>T		intron	N/A	NP_000860.3	P46098-1
	HTR3A	NM_001161772.3		c.-4A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001155244.1	P46098-3
	HTR3A	NM_001161772.3		c.-4A>T		5_prime_UTR	Exon 1 of 9	NP_001155244.1	P46098-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR3A	ENST00000504030.7	TSL:1 MANE Select	c.68-220A>T		intron	N/A	ENSP00000424189.2	P46098-1
	HTR3A	ENST00000375498.6	TSL:1	c.86-220A>T		intron	N/A	ENSP00000364648.2	P46098-4
	HTR3A	ENST00000299961.5	TSL:2	c.-4A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000299961.4	P46098-3

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

GnomAD2 exomes AF: 0.626 AC: 96807 AN: 154570 AF XY: 0.639

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 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

African (AFR) AF: 0.322 AC: 10146 AN: 31546

American (AMR) AF: 0.536 AC: 19128 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 17356 AN: 25150

East Asian (EAS) AF: 0.690 AC: 24635 AN: 35720

South Asian (SAS) AF: 0.695 AC: 54969 AN: 79142

European-Finnish (FIN) AF: 0.611 AC: 30022 AN: 49122

Middle Eastern (MID) AF: 0.706 AC: 4015 AN: 5684

European-Non Finnish (NFE) AF: 0.682 AC: 734015 AN: 1076190

Other (OTH) AF: 0.649 AC: 37583 AN: 57902

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

African (AFR) AF: 0.338 AC: 14009 AN: 41438

American (AMR) AF: 0.578 AC: 8838 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2392 AN: 3468

East Asian (EAS) AF: 0.654 AC: 3381 AN: 5170

South Asian (SAS) AF: 0.685 AC: 3307 AN: 4826

European-Finnish (FIN) AF: 0.606 AC: 6399 AN: 10552

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45853 AN: 67970

Other (OTH) AF: 0.593 AC: 1252 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.36
PhyloP100		-0.74
PromoterAI		0.0062	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1985242; hg19: chr11-113848273;