rs3762528

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000751.3(CHRND):c.1047+9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 1,608,224 control chromosomes in the GnomAD database, including 3,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 430 hom., cov: 30)

Exomes 𝑓: 0.067 ( 3418 hom. )

Consequence

CHRND
NM_000751.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.341

Publications

13 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
congenital myasthenic syndrome 3B
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
congenital myasthenic syndrome 3C
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
lethal multiple pterygium syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-232531665-T-C is Benign according to our data. Variant chr2-232531665-T-C is described in ClinVar as Benign. ClinVar VariationId is 128755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000751.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRND	NM_000751.3	MANE Select	c.1047+9T>C	intron	N/A	NP_000742.1	Q07001-1
CHRND	NM_001256657.2		c.1002+9T>C	intron	N/A	NP_001243586.1	Q07001-2
CHRND	NM_001311196.2		c.744+9T>C	intron	N/A	NP_001298125.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRND	ENST00000258385.8	TSL:1 MANE Select	c.1047+9T>C	intron	N/A	ENSP00000258385.3	Q07001-1
CHRND	ENST00000543200.5	TSL:2	c.1002+9T>C	intron	N/A	ENSP00000438380.1	Q07001-2
CHRND	ENST00000955151.1		c.846+9T>C	intron	N/A	ENSP00000625210.1

Frequencies

GnomAD3 genomes

AF:

0.0726

AC:

11037

AN:

152012

Hom.:

429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0837

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0501

Gnomad EAS

AF:

0.0753

Gnomad SAS

AF:

0.0549

Gnomad FIN

AF:

0.0581

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0639

Gnomad OTH

AF:

0.0642

GnomAD2 exomes

AF:

0.0693

AC:

17281

AN:

249274

AF XY:

0.0668

show subpopulations

Gnomad AFR exome

AF:

0.0856

Gnomad AMR exome

AF:

0.0991

Gnomad ASJ exome

AF:

0.0472

Gnomad EAS exome

AF:

0.0748

Gnomad FIN exome

AF:

0.0600

Gnomad NFE exome

AF:

0.0633

Gnomad OTH exome

AF:

0.0684

GnomAD4 exome

AF:

0.0672

AC:

97806

AN:

1456094

Hom.:

3418

Cov.:

AF XY:

0.0663

AC XY:

48075

AN XY:

724758

show subpopulations

African (AFR)

AF:

0.0862

AC:

2880

AN:

33402

American (AMR)

AF:

0.0978

AC:

4375

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0495

AC:

1293

AN:

26116

East Asian (EAS)

AF:

0.0705

AC:

2798

AN:

39686

South Asian (SAS)

AF:

0.0588

AC:

5072

AN:

86190

European-Finnish (FIN)

AF:

0.0606

AC:

3095

AN:

51112

Middle Eastern (MID)

AF:

0.0636

AC:

366

AN:

5752

European-Non Finnish (NFE)

AF:

0.0666

AC:

73880

AN:

1108860

Other (OTH)

AF:

0.0672

AC:

4047

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

4749

9497

14246

18994

23743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2766

5532

8298

11064

13830

<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:

0.0726

AC:

11045

AN:

152130

Hom.:

430

Cov.:

AF XY:

0.0727

AC XY:

5410

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0838

AC:

3479

AN:

41496

American (AMR)

AF:

0.100

AC:

1535

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0501

AC:

174

AN:

3472

East Asian (EAS)

AF:

0.0751

AC:

388

AN:

5164

South Asian (SAS)

AF:

0.0545

AC:

263

AN:

4822

European-Finnish (FIN)

AF:

0.0581

AC:

616

AN:

10594

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0639

AC:

4343

AN:

67980

Other (OTH)

AF:

0.0631

AC:

133

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

510

1020

1530

2040

2550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0666

Hom.:

381

Bravo

AF:

0.0757

Asia WGS

AF:

0.0700

AC:

246

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Lethal multiple pterygium syndrome (2)

Congenital myasthenic syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

(source)

DANN

Benign

0.58

PhyloP100

-0.34

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over