chr4-40348938-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_017581.4(CHRNA9):c.422G>A(p.Gly141Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,614,140 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00093 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 4 hom. )
Consequence
CHRNA9
NM_017581.4 missense
NM_017581.4 missense
Scores
15
3
1
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
CHRNA9 (HGNC:14079): (cholinergic receptor nicotinic alpha 9 subunit) This gene is a member of the ligand-gated ionic channel family and nicotinic acetylcholine receptor gene superfamily. It encodes a plasma membrane protein that forms homo- or hetero-oligomeric divalent cation channels. This protein is involved in cochlea hair cell development and is also expressed in the outer hair cells (OHCs) of the adult cochlea. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA9 | NM_017581.4 | c.422G>A | p.Gly141Glu | missense_variant | 4/5 | ENST00000310169.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA9 | ENST00000310169.3 | c.422G>A | p.Gly141Glu | missense_variant | 4/5 | 1 | NM_017581.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000927 AC: 141AN: 152168Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000812 AC: 204AN: 251222Hom.: 0 AF XY: 0.000862 AC XY: 117AN XY: 135782
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GnomAD4 exome AF: 0.00117 AC: 1717AN: 1461854Hom.: 4 Cov.: 31 AF XY: 0.00123 AC XY: 891AN XY: 727236
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GnomAD4 genome AF: 0.000932 AC: 142AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.000846 AC XY: 63AN XY: 74462
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 09, 2022 | The c.422G>A (p.G141E) alteration is located in exon 4 (coding exon 4) of the CHRNA9 gene. This alteration results from a G to A substitution at nucleotide position 422, causing the glycine (G) at amino acid position 141 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at