Variant chr11-113981322-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000869.6(HTR3A):c.374+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,551,966 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 6 hom. )

Consequence

HTR3A
NM_000869.6 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.450

Variant links:

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]

HTR3A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-113981322-G-A is Benign according to our data. Variant chr11-113981322-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 714264.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-113981322-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
HTR3A	NM_000869.6 linkuse as main transcript	c.374+10G>A	intron_variant	ENST00000504030.7
HTR3A	NM_001161772.3 linkuse as main transcript	c.329+10G>A	intron_variant
HTR3A	NM_213621.4 linkuse as main transcript	c.374+10G>A	intron_variant
HTR3A	NR_046363.2 linkuse as main transcript	n.592+10G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR3A	ENST00000504030.7 linkuse as main transcript	c.374+10G>A		intron_variant		1	NM_000869.6	P1	P46098-1

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

194

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00210

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00119

AC:

299

AN:

251280

Hom.:

AF XY:

0.00137

AC XY:

186

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00209

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00180

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00178

AC:

2486

AN:

1399680

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

1270

AN XY:

699900

show subpopulations

Gnomad4 AFR exome

AF:

0.0000621

Gnomad4 AMR exome

AF:

0.000762

Gnomad4 ASJ exome

AF:

0.000737

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00171

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00206

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00127

AC:

194

AN:

152286

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00210

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00145

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.70

DANN

Benign

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over