chr2-232525995-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000441621.6(CHRND):c.-221C>T variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 474,730 control chromosomes in the GnomAD database, including 210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.027 ( 85 hom., cov: 29)
Exomes 𝑓: 0.014 ( 125 hom. )
Consequence
CHRND
ENST00000441621.6 5_prime_UTR, NMD_transcript
ENST00000441621.6 5_prime_UTR, NMD_transcript
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0860
Genes affected
CHRND (HGNC:1965): (cholinergic receptor nicotinic delta subunit) The acetylcholine receptor of muscle has 5 subunits of 4 different types: 2 alpha and 1 each of beta, gamma and delta subunits. After acetylcholine binding, the receptor undergoes an extensive conformation change that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. Defects in this gene are a cause of multiple pterygium syndrome lethal type (MUPSL), congenital myasthenic syndrome slow-channel type (SCCMS), and congenital myasthenic syndrome fast-channel type (FCCMS). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 2-232525995-C-T is Benign according to our data. Variant chr2-232525995-C-T is described in ClinVar as [Benign]. Clinvar id is 1247861.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.027 (4096/151636) while in subpopulation NFE AF= 0.041 (2777/67766). AF 95% confidence interval is 0.0397. There are 85 homozygotes in gnomad4. There are 2056 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 85 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRND | ENST00000441621.6 | c.-221C>T | 5_prime_UTR_variant, NMD_transcript_variant | 1/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0270 AC: 4095AN: 151526Hom.: 85 Cov.: 29
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GnomAD4 exome AF: 0.0139 AC: 4482AN: 323094Hom.: 125 Cov.: 3 AF XY: 0.0134 AC XY: 2301AN XY: 171080
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GnomAD4 genome ? AF: 0.0270 AC: 4096AN: 151636Hom.: 85 Cov.: 29 AF XY: 0.0278 AC XY: 2056AN XY: 74078
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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 submitter | clinical testing | GeneDx | Jul 08, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at