2-232532815-T-G

Position:

• chr2-232532815-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000751.3(CHRND):​c.1048-1116T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,120 control chromosomes in the GnomAD database, including 4,566 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 0.23 (4566 hom., cov: 32)
• Consequence: CHRND NM_000751.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRND	NM_000751.3	c.1048-1116T>G		intron_variant		ENST00000258385.8
CHRND	NM_001256657.2	c.1003-1116T>G		intron_variant
CHRND	NM_001311195.2	c.466-1116T>G		intron_variant
CHRND	NM_001311196.2	c.745-1116T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRND	ENST00000258385.8	c.1048-1116T>G		intron_variant		1	NM_000751.3	P1
CHRND	ENST00000543200.5	c.1003-1116T>G		intron_variant		2
CHRND	ENST00000441621.6	c.*230-1116T>G		intron_variant, NMD_transcript_variant		5
CHRND	ENST00000446616.1	c.*689-1116T>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34641 AN: 152000 Hom.: 4544 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.228 AC: 34679 AN: 152120 Hom.: 4566 Cov.: 32 AF XY: 0.231 AC XY: 17154 AN XY: 74352

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.251

Alfa AF: 0.190 Hom.: 747

Bravo AF: 0.235

Asia WGS AF: 0.387 AC: 1343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.71

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: rs12466358; hg19: chr2-233397525;