17-4899483-G-C

Variant names:

• chr17-4899483-G-C
• rs114454383
• NM_000080.4:c.1017C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000080.4(CHRNE):​c.1017C>G​(p.Ser339Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,598,656 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S339S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0084 (17 hom., cov: 33)
  • Exomes 𝑓: 0.00093 (16 hom.)
• Consequence: CHRNE NM_000080.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.817
• 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]

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=-0.58).
• BP6: Variant 17-4899483-G-C is Benign according to our data. Variant chr17-4899483-G-C is described in ClinVar as Benign. ClinVar VariationId is 128760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.817 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00841 (1281/152262) while in subpopulation AFR AF = 0.0293 (1216/41556). AF 95% confidence interval is 0.0279. There are 17 homozygotes in GnomAd4. There are 589 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AR,AD gene

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.1017C>G	p.Ser339Ser	synonymous	Exon 9 of 12	NP_000071.1	Q04844
	C17orf107	NM_001145536.2	MANE Select	c.-280G>C		upstream_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.1017C>G	p.Ser339Ser	synonymous	Exon 9 of 12	ENSP00000497829.1	Q04844
	C17orf107	ENST00000521575.1	TSL:1	c.-280G>C		5_prime_UTR	Exon 1 of 2	ENSP00000429241.1	E5RJ01
	CHRNE	ENST00000649830.1		c.84C>G	p.Ser28Ser	synonymous	Exon 9 of 11	ENSP00000496907.1	A0A3B3IRM1

Frequencies

GnomAD3 genomes AF: 0.00837 AC: 1274 AN: 152144 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00479

GnomAD2 exomes AF: 0.00237 AC: 528 AN: 222638 AF XY: 0.00169

Gnomad AFR exome AF: 0.0317

Gnomad AMR exome AF: 0.00291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000302

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.000926 AC: 1340 AN: 1446394 Hom.: 16 Cov.: 34 AF XY: 0.000807 AC XY: 579 AN XY: 717850

African (AFR) AF: 0.0315 AC: 1049 AN: 33322

American (AMR) AF: 0.00286 AC: 122 AN: 42598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25650

East Asian (EAS) AF: 0.00 AC: 0 AN: 39166

South Asian (SAS) AF: 0.000132 AC: 11 AN: 83282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50926

Middle Eastern (MID) AF: 0.000913 AC: 5 AN: 5478

European-Non Finnish (NFE) AF: 0.0000172 AC: 19 AN: 1106206

Other (OTH) AF: 0.00224 AC: 134 AN: 59766

GnomAD4 genome AF: 0.00841 AC: 1281 AN: 152262 Hom.: 17 Cov.: 33 AF XY: 0.00791 AC XY: 589 AN XY: 74444

African (AFR) AF: 0.0293 AC: 1216 AN: 41556

American (AMR) AF: 0.00327 AC: 50 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68014

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.000583 Hom.: 0

Bravo AF: 0.0103

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.8
DANN	Benign	0.72
PhyloP100		0.82
PromoterAI		0.26	Neutral
Mutation Taster		=293/7	polymorphism

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: rs114454383; hg19: chr17-4802778;