rs3791729

Positions:

• chr2-232530587-G-A
• chr2-232530587-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRND	NM_000751.3	c.820+448G>A		intron_variant		ENST00000258385.8
CHRND	NM_001256657.2	c.775+448G>A		intron_variant
CHRND	NM_001311195.2	c.239-765G>A		intron_variant
CHRND	NM_001311196.2	c.517+448G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRND	ENST00000258385.8	c.820+448G>A		intron_variant		1	NM_000751.3	P1

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

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.308

Alfa AF: 0.334 Hom.: 5668

Bravo AF: 0.300

Asia WGS AF: 0.455 AC: 1582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs3791729; hg19: chr2-233395297;