rs34563587

Variant names:

• chr17-4903019-G-A
• rs34563587
• NM_000080.4:c.45C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-4903019-G-A
• chr17-4903019-G-C
• chr17-4903019-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000080.4(CHRNE):​c.45C>T​(p.Leu15Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00569 in 1,613,954 control chromosomes in the GnomAD database, including 210 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (100 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (110 hom.)
• Consequence: CHRNE NM_000080.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.0007810
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -3.26
• Publications: 7 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]

C17orf107 (HGNC:37238): (chromosome 17 open reading frame 107)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 17-4903019-G-A is Benign according to our data. Variant chr17-4903019-G-A is described in ClinVar as Benign. ClinVar VariationId is 128766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0653 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.45C>T	p.Leu15Leu	splice_region synonymous	Exon 1 of 12	NP_000071.1	Q04844
	C17orf107	NM_001145536.2	MANE Select	c.*2486G>A		downstream_gene	N/A	NP_001139008.1	Q6ZR85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNE	ENST00000649488.2	MANE Select	c.45C>T	p.Leu15Leu	splice_region synonymous	Exon 1 of 12	ENSP00000497829.1	Q04844
	CHRNE	ENST00000649830.1		c.-887-256C>T		intron	N/A	ENSP00000496907.1	A0A3B3IRM1
	C17orf107	ENST00000381365.4	TSL:2 MANE Select	c.*2486G>A		downstream_gene	N/A	ENSP00000370770.3	Q6ZR85

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 3296 AN: 151978 Hom.: 100 Cov.: 32

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00221

Gnomad OTH AF: 0.0287

GnomAD2 exomes AF: 0.00747 AC: 1878 AN: 251398 AF XY: 0.00635

Gnomad AFR exome AF: 0.0683

Gnomad AMR exome AF: 0.00810

Gnomad ASJ exome AF: 0.0136

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00232

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.00402 AC: 5876 AN: 1461858 Hom.: 110 Cov.: 32 AF XY: 0.00380 AC XY: 2762 AN XY: 727230

African (AFR) AF: 0.0703 AC: 2352 AN: 33478

American (AMR) AF: 0.00903 AC: 404 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 355 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000916 AC: 79 AN: 86250

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53414

Middle Eastern (MID) AF: 0.0153 AC: 88 AN: 5768

European-Non Finnish (NFE) AF: 0.00183 AC: 2030 AN: 1111992

Other (OTH) AF: 0.00932 AC: 563 AN: 60396

GnomAD4 genome AF: 0.0217 AC: 3302 AN: 152096 Hom.: 100 Cov.: 32 AF XY: 0.0212 AC XY: 1578 AN XY: 74356

African (AFR) AF: 0.0674 AC: 2796 AN: 41468

American (AMR) AF: 0.0154 AC: 235 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4804

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10596

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

European-Non Finnish (NFE) AF: 0.00221 AC: 150 AN: 67998

Other (OTH) AF: 0.0284 AC: 60 AN: 2112

Alfa AF: 0.00939 Hom.: 99

Bravo AF: 0.0248

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.00322

EpiControl AF: 0.00255

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Congenital myasthenic syndrome (2)
-	-	2	not provided (2)
-	-	1	Congenital myasthenic syndrome 4A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.052
DANN	Benign	0.84
PhyloP100		-3.3
PromoterAI		0.011	Neutral
Mutation Taster		=71/29	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00078
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.11		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: rs34563587; hg19: chr17-4806314;