chr17-4898693-A-G

Variant names:

• chr17-4898693-A-G
• rs2229200
• NM_000080.4:c.*43T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000080.4(CHRNE):​c.*43T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00812 in 1,589,882 control chromosomes in the GnomAD database, including 459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (219 hom., cov: 33)
  • Exomes 𝑓: 0.0055 (240 hom.)
• Consequence: CHRNE NM_000080.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.92
• Publications: 2 publications found

Genes affected

CHRNE (HGNC:1966): (cholinergic receptor nicotinic epsilon subunit) Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]

CHRNE Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina
• congenital myasthenic syndrome 4A

  Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• congenital myasthenic syndrome 4B

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• congenital myasthenic syndrome 4C

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• postsynaptic congenital myasthenic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-4898693-A-G is Benign according to our data. Variant chr17-4898693-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 254885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000080.4. 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
	CHRNE	NM_000080.4	MANE Select	c.*43T>C		3_prime_UTR	Exon 12 of 12	NP_000071.1	Q04844

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNE	ENST00000649488.2	MANE Select	c.*43T>C		3_prime_UTR	Exon 12 of 12	ENSP00000497829.1	Q04844
	CHRNE	ENST00000649830.1		c.*161T>C		3_prime_UTR	Exon 11 of 11	ENSP00000496907.1	A0A3B3IRM1
	CHRNE	ENST00000572438.1	TSL:5	n.1211T>C		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4975 AN: 152024 Hom.: 219 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0187

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00254

Gnomad OTH AF: 0.0325

GnomAD2 exomes AF: 0.0107 AC: 2273 AN: 212434 AF XY: 0.00878

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.0109

Gnomad ASJ exome AF: 0.0218

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00266

Gnomad OTH exome AF: 0.0145

GnomAD4 exome AF: 0.00551 AC: 7928 AN: 1437740 Hom.: 240 Cov.: 33 AF XY: 0.00509 AC XY: 3629 AN XY: 712758

African (AFR) AF: 0.112 AC: 3738 AN: 33314

American (AMR) AF: 0.0121 AC: 484 AN: 39916

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 590 AN: 25542

East Asian (EAS) AF: 0.00 AC: 0 AN: 38962

South Asian (SAS) AF: 0.000460 AC: 38 AN: 82626

European-Finnish (FIN) AF: 0.0000789 AC: 4 AN: 50684

Middle Eastern (MID) AF: 0.0179 AC: 102 AN: 5712

European-Non Finnish (NFE) AF: 0.00202 AC: 2226 AN: 1101358

Other (OTH) AF: 0.0125 AC: 746 AN: 59626

GnomAD4 genome AF: 0.0328 AC: 4983 AN: 152142 Hom.: 219 Cov.: 33 AF XY: 0.0316 AC XY: 2350 AN XY: 74376

African (AFR) AF: 0.105 AC: 4363 AN: 41502

American (AMR) AF: 0.0187 AC: 285 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10608

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00255 AC: 173 AN: 67970

Other (OTH) AF: 0.0322 AC: 68 AN: 2112

Alfa AF: 0.0108 Hom.: 13

Bravo AF: 0.0374

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital myasthenic syndrome (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.24
PhyloP100		-3.9
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: rs2229200; hg19: chr17-4801988;