Variant 2-232525995-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0860

Variant links:

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]

CHRND links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 85 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRND	ENST00000441621.6 linkuse as main transcript	c.-221C>T		5_prime_UTR_variant, NMD_transcript_variant	1/11	5		ENSP00000408819

Frequencies

GnomAD3 genomes

AF:

0.0270

AC:

4095

AN:

151526

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00611

Gnomad AMI

AF:

0.0133

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.000391

Gnomad SAS

AF:

0.0102

Gnomad FIN

AF:

0.0617

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0410

Gnomad OTH

AF:

0.0227

GnomAD4 exome

AF:

0.0139

AC:

4482

AN:

323094

Hom.:

125

Cov.:

AF XY:

0.0134

AC XY:

2301

AN XY:

171080

show subpopulations

Gnomad4 AFR exome

AF:

0.00270

Gnomad4 AMR exome

AF:

0.00359

Gnomad4 ASJ exome

AF:

0.00824

Gnomad4 EAS exome

AF:

0.0000452

Gnomad4 SAS exome

AF:

0.00596

Gnomad4 FIN exome

AF:

0.0265

Gnomad4 NFE exome

AF:

0.0170

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.0270

AC:

4096

AN:

151636

Hom.:

Cov.:

AF XY:

0.0278

AC XY:

2056

AN XY:

74078

show subpopulations

Gnomad4 AFR

AF:

0.00609

Gnomad4 AMR

AF:

0.0156

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.000392

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.0617

Gnomad4 NFE

AF:

0.0410

Gnomad4 OTH

AF:

0.0224

Alfa

AF:

0.0399

Hom.:

Bravo

AF:

0.0223

Asia WGS

AF:

0.00725

AC:

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.3

DANN

Benign

0.79

Splicing

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