ENST00000442996.1:n.322-676A>G

Variant names:

• chr2-174772073-A-G
• rs935863
• ENST00000442996.1:n.322-676A>G

Variant summary

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

The ENST00000442996.1(ENSG00000236449):​n.322-676A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,986 control chromosomes in the GnomAD database, including 12,659 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 0.40 (12659 hom., cov: 32)
• Consequence: ENSG00000236449 ENST00000442996.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 5 publications found

Genes affected

ENSG00000236449 (HGNC:):

CHRNA1 (HGNC:1955): (cholinergic receptor nicotinic alpha 1 subunit) The muscle acetylcholine receptor consiststs of 5 subunits of 4 different types: 2 alpha subunits and 1 each of the beta, gamma, and delta subunits. This gene encodes an alpha subunit that plays a role in acetlycholine binding/channel gating. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2012]

CHRNA1 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 1A

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• myasthenic syndrome, congenital, 1B, fast-channel

  Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• lethal multiple pterygium syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000442996.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000236449	ENST00000442996.1	TSL:1	n.322-676A>G		intron	N/A
	CHRNA1	ENST00000636168.2	TSL:5	c.-447+4032T>C		intron	N/A	ENSP00000490338.2	A0A1B0GV17
	ENSG00000236449	ENST00000654673.1		n.285A>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60824 AN: 151868 Hom.: 12643 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.401 AC: 60883 AN: 151986 Hom.: 12659 Cov.: 32 AF XY: 0.408 AC XY: 30318 AN XY: 74272

African (AFR) AF: 0.453 AC: 18746 AN: 41426

American (AMR) AF: 0.423 AC: 6461 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 944 AN: 3468

East Asian (EAS) AF: 0.684 AC: 3530 AN: 5164

South Asian (SAS) AF: 0.455 AC: 2193 AN: 4824

European-Finnish (FIN) AF: 0.412 AC: 4338 AN: 10538

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23642 AN: 67964

Other (OTH) AF: 0.370 AC: 782 AN: 2114

Alfa AF: 0.353 Hom.: 15772

Bravo AF: 0.404

Asia WGS AF: 0.541 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.7
DANN	Benign	0.66
PhyloP100		0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs935863; hg19: chr2-175636801;