2-232530587-G-A

Variant names:

• chr2-232530587-G-A
• rs3791729
• NM_000751.3:c.820+448G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000751.3(CHRND):​c.820+448G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,056 control chromosomes in the GnomAD database, including 7,542 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7542 hom., cov: 32)
• Consequence: CHRND NM_000751.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.424 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRND	NM_000751.3	MANE Select	c.820+448G>A		intron	N/A	NP_000742.1
	CHRND	NM_001256657.2		c.775+448G>A		intron	N/A	NP_001243586.1
	CHRND	NM_001311196.2		c.517+448G>A		intron	N/A	NP_001298125.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRND	ENST00000258385.8	TSL:1 MANE Select	c.820+448G>A		intron	N/A	ENSP00000258385.3
	CHRND	ENST00000543200.5	TSL:2	c.775+448G>A		intron	N/A	ENSP00000438380.1
	CHRND	ENST00000412233.5	TSL:4	n.510-765G>A		intron	N/A	ENSP00000398143.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44588 AN: 151938 Hom.: 7524 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.302

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44626 AN: 152056 Hom.: 7542 Cov.: 32 AF XY: 0.297 AC XY: 22084 AN XY: 74320

African (AFR) AF: 0.132 AC: 5489 AN: 41520

American (AMR) AF: 0.433 AC: 6606 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1223 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2219 AN: 5136

South Asian (SAS) AF: 0.412 AC: 1980 AN: 4802

European-Finnish (FIN) AF: 0.295 AC: 3127 AN: 10584

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22866 AN: 67962

Other (OTH) AF: 0.308 AC: 649 AN: 2106

Alfa AF: 0.334 Hom.: 9086

Bravo AF: 0.300

Asia WGS AF: 0.455 AC: 1582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.66
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3791729; hg19: chr2-233395297;