2-232526227-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000751.3(CHRND):c.12A>G(p.Pro4Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,587,830 control chromosomes in the GnomAD database, including 189,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16495 hom., cov: 31)

Exomes 𝑓: 0.49 ( 172766 hom. )

Consequence

CHRND
NM_000751.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.34

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-232526227-A-G is Benign according to our data. Variant chr2-232526227-A-G is described in ClinVar as [Benign]. Clinvar id is 128757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232526227-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRND	NM_000751.3 link	c.12A>G	p.Pro4Pro	synonymous_variant	Exon 1 of 12	ENST00000258385.8	NP_000742.1	Q07001-1
CHRND	NM_001256657.2 link	c.12A>G	p.Pro4Pro	synonymous_variant	Exon 1 of 11		NP_001243586.1	Q07001-2
CHRND	NM_001311196.2 link	c.-260A>G		5_prime_UTR_variant	Exon 1 of 12		NP_001298125.1	Q07001
CHRND	NM_001311195.2 link	c.-260A>G		5_prime_UTR_variant	Exon 1 of 10		NP_001298124.1	Q07001B4E3W4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRND	ENST00000258385.8 link	c.12A>G	p.Pro4Pro	synonymous_variant	Exon 1 of 12	1	NM_000751.3	ENSP00000258385.3		Q07001-1

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

69913

AN:

150440

Hom.:

16475

Cov.:

show subpopulations

Gnomad AFR

AF:

0.385

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.688

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.518

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.437

GnomAD3 exomes

AF:

0.504

AC:

125831

AN:

249842

Hom.:

32418

AF XY:

0.502

AC XY:

67874

AN XY:

135186

show subpopulations

Gnomad AFR exome

AF:

0.378

Gnomad AMR exome

AF:

0.551

Gnomad ASJ exome

AF:

0.499

Gnomad EAS exome

AF:

0.693

Gnomad SAS exome

AF:

0.490

Gnomad FIN exome

AF:

0.495

Gnomad NFE exome

AF:

0.484

Gnomad OTH exome

AF:

0.472

GnomAD4 exome

AF:

0.492

AC:

707422

AN:

1437272

Hom.:

172766

Cov.:

AF XY:

0.493

AC XY:

352450

AN XY:

714824

show subpopulations

Gnomad4 AFR exome

AF:

0.383

Gnomad4 AMR exome

AF:

0.554

Gnomad4 ASJ exome

AF:

0.513

Gnomad4 EAS exome

AF:

0.656

Gnomad4 SAS exome

AF:

0.496

Gnomad4 FIN exome

AF:

0.518

Gnomad4 NFE exome

AF:

0.485

Gnomad4 OTH exome

AF:

0.494

GnomAD4 genome

AF:

0.465

AC:

69978

AN:

150558

Hom.:

16495

Cov.:

AF XY:

0.468

AC XY:

34424

AN XY:

73528

show subpopulations

Gnomad4 AFR

AF:

0.385

Gnomad4 AMR

AF:

0.475

Gnomad4 ASJ

AF:

0.486

Gnomad4 EAS

AF:

0.687

Gnomad4 SAS

AF:

0.517

Gnomad4 FIN

AF:

0.518

Gnomad4 NFE

AF:

0.484

Gnomad4 OTH

AF:

0.442

Alfa

AF:

0.472

Hom.:

19484

Bravo

AF:

0.458

Asia WGS

AF:

0.574

AC:

1992

AN:

3478

EpiCase

AF:

0.479

EpiControl

AF:

0.478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Dec 09, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 19, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lethal multiple pterygium syndrome

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital myasthenic syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: 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

-0.85

CADD

Benign

0.46

DANN

Benign

0.79

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

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