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GeneBe

8-42756401-C-T

Variant summary

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

The NM_004198.3(CHRNA6):c.798G>A(p.Ser266=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000955 in 1,613,944 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00054 ( 7 hom. )

Consequence

CHRNA6
NM_004198.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.66
Variant links:
Genes affected
CHRNA6 (HGNC:15963): (cholinergic receptor nicotinic alpha 6 subunit) This gene encodes an alpha subunit of neuronal nicotinic acetylcholine receptors. These receptors consist of five subunits and function as ion channels involved in neurotransmission. The encoded protein is a subunit of neuronal nicotinic acetylcholine receptors that mediate dopaminergic neurotransmission and are activated by acetylcholine and exogenous nicotine. Alternatively spliced transcript variants have been observed for this gene. Single nucleotide polymorphisms in this gene have been associated with both nicotine and alcohol dependence. [provided by RefSeq, Dec 2010]

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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=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-42756401-C-T is Benign according to our data. Variant chr8-42756401-C-T is described in ClinVar as [Benign]. Clinvar id is 788868.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=-1.65 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 = 0.00497 (756/152060) while in subpopulation AFR AF= 0.0172 (712/41478). AF 95% confidence interval is 0.0161. There are 5 homozygotes in gnomad4. There are 373 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 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHRNA6NM_004198.3 linkuse as main transcriptc.798G>A p.Ser266= synonymous_variant 5/6 ENST00000276410.7
CHRNA6NM_001199279.1 linkuse as main transcriptc.753G>A p.Ser251= synonymous_variant 4/5
CHRNA6XM_047422396.1 linkuse as main transcriptc.798G>A p.Ser266= synonymous_variant 6/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHRNA6ENST00000276410.7 linkuse as main transcriptc.798G>A p.Ser266= synonymous_variant 5/61 NM_004198.3 P1Q15825-1
CHRNA6ENST00000534622.5 linkuse as main transcriptc.753G>A p.Ser251= synonymous_variant 4/52 Q15825-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00493
AC:
749
AN:
151942
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0170
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00157
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000736
Gnomad OTH
AF:
0.00670
GnomAD3 exomes
AF:
0.00129
AC:
324
AN:
251444
Hom.:
1
AF XY:
0.000876
AC XY:
119
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.0180
Gnomad AMR exome
AF:
0.000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000615
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000537
AC:
785
AN:
1461884
Hom.:
7
Cov.:
33
AF XY:
0.000465
AC XY:
338
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0194
Gnomad4 AMR exome
AF:
0.000626
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.00113
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00497
AC:
756
AN:
152060
Hom.:
5
Cov.:
32
AF XY:
0.00502
AC XY:
373
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0172
Gnomad4 AMR
AF:
0.00157
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000736
Gnomad4 OTH
AF:
0.00664
Alfa
AF:
0.00229
Hom.:
0
Bravo
AF:
0.00543
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

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 testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
4.9
Dann
Benign
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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: rs78464081; hg19: chr8-42611544; COSMIC: COSV52380663; COSMIC: COSV52380663; API