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GeneBe

1-19666017-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000871.3(HTR6):c.264G>A(p.Leu88=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,613,852 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 12 hom., cov: 32)
Exomes 𝑓: 0.00065 ( 8 hom. )

Consequence

HTR6
NM_000871.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.55
Variant links:
Genes affected
HTR6 (HGNC:5301): (5-hydroxytryptamine receptor 6) This gene encodes a protein that belongs to the seven-transmembrane G protein-coupled receptor family of proteins. The encoded protein couples with the Gs alpha subunit and stimulates adenylate cyclase to activate the cyclic AMP-dependent signaling pathway. This receptor is thought to regulate cholinergic neuronal transmission in the brain. Several antidepressants and antipsychotic drugs have a high affinity for this receptor. [provided by RefSeq, Aug 2013]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-19666017-G-A is Benign according to our data. Variant chr1-19666017-G-A is described in ClinVar as [Benign]. Clinvar id is 780219.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.55 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00687 (1046/152366) while in subpopulation AFR AF= 0.0243 (1010/41582). AF 95% confidence interval is 0.023. There are 12 homozygotes in gnomad4. There are 505 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 12 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HTR6NM_000871.3 linkuse as main transcriptc.264G>A p.Leu88= synonymous_variant 1/3 ENST00000289753.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HTR6ENST00000289753.2 linkuse as main transcriptc.264G>A p.Leu88= synonymous_variant 1/31 NM_000871.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00686
AC:
1045
AN:
152248
Hom.:
12
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00157
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00167
AC:
418
AN:
250204
Hom.:
4
AF XY:
0.00119
AC XY:
161
AN XY:
135442
show subpopulations
Gnomad AFR exome
AF:
0.0242
Gnomad AMR exome
AF:
0.000695
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000492
GnomAD4 exome
AF:
0.000646
AC:
944
AN:
1461486
Hom.:
8
Cov.:
32
AF XY:
0.000565
AC XY:
411
AN XY:
727096
show subpopulations
Gnomad4 AFR exome
AF:
0.0248
Gnomad4 AMR exome
AF:
0.000917
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00109
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00687
AC:
1046
AN:
152366
Hom.:
12
Cov.:
32
AF XY:
0.00678
AC XY:
505
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0243
Gnomad4 AMR
AF:
0.00157
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00425
Alfa
AF:
0.000913
Hom.:
2
Bravo
AF:
0.00767
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
Cadd
Benign
8.8
Dann
Benign
0.96

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.

Other links and lift over

dbSNP: rs111648246; hg19: chr1-19992510; API