2-232535288-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1

The NM_000751.3(CHRND):c.1530C>T(p.Asn510Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 1,613,960 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

CHRND
NM_000751.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -4.24

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 3A
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
congenital myasthenic syndrome 3B
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp
congenital myasthenic syndrome 3C
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
lethal multiple pterygium syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHRND links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 2-232535288-C-T is Benign according to our data. Variant chr2-232535288-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 288058.

BP7

Synonymous conserved (PhyloP=-4.24 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00157 (239/152348) while in subpopulation AFR AF = 0.00524 (218/41580). AF 95% confidence interval is 0.00467. There are 0 homozygotes in GnomAd4. There are 94 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CHRND	NM_000751.3 link	c.1530C>T	p.Asn510Asn	synonymous_variant	Exon 12 of 12	ENST00000258385.8	NP_000742.1
CHRND	NM_001256657.2 link	c.1485C>T	p.Asn495Asn	synonymous_variant	Exon 11 of 11		NP_001243586.1
CHRND	NM_001311196.2 link	c.1227C>T	p.Asn409Asn	synonymous_variant	Exon 12 of 12		NP_001298125.1
CHRND	NM_001311195.2 link	c.948C>T	p.Asn316Asn	synonymous_variant	Exon 10 of 10		NP_001298124.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRND	ENST00000258385.8 link	c.1530C>T	p.Asn510Asn	synonymous_variant	Exon 12 of 12	1	NM_000751.3	ENSP00000258385.3

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

238

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00523

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.00335

GnomAD2 exomes

AF:

0.000438

AC:

110

AN:

251216

AF XY:

0.000324

show subpopulations

Gnomad AFR exome

AF:

0.00541

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000200

AC:

292

AN:

1461612

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

128

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.00562

AC:

188

AN:

33480

American (AMR)

AF:

0.000537

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53144

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000405

AC:

AN:

1112010

Other (OTH)

AF:

0.000513

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00157

AC:

239

AN:

152348

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00524

AC:

218

AN:

41580

American (AMR)

AF:

0.000719

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68038

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000602

Hom.:

Bravo

AF:

0.00192

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Lethal multiple pterygium syndrome

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Uncertain:1

Jun 03, 2016

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Congenital myasthenic syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.048

(source)

DANN

Benign

0.63

PhyloP100

-4.2

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over