rs33970119

Variant names:

• chr17-4901607-G-A
• rs33970119
• NM_000080.4:c.519C>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.519C>T​(p.Ala173Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0518 in 1,613,756 control chromosomes in the GnomAD database, including 2,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (169 hom., cov: 33)
  • Exomes 𝑓: 0.053 (2375 hom.)
• Consequence: CHRNE NM_000080.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.314
• Publications: 9 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=-0.64).
• BP6: Variant 17-4901607-G-A is Benign according to our data. Variant chr17-4901607-G-A is described in ClinVar as Benign. ClinVar VariationId is 128767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.314 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0594 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.519C>T	p.Ala173Ala	synonymous	Exon 6 of 12	NP_000071.1	Q04844
	C17orf107	NM_001145536.2	MANE Select	c.*1074G>A		3_prime_UTR	Exon 3 of 3	NP_001139008.1	Q6ZR85

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNE	ENST00000649488.2	MANE Select	c.519C>T	p.Ala173Ala	synonymous	Exon 6 of 12	ENSP00000497829.1	Q04844
	C17orf107	ENST00000381365.4	TSL:2 MANE Select	c.*1074G>A		3_prime_UTR	Exon 3 of 3	ENSP00000370770.3	Q6ZR85
	CHRNE	ENST00000649830.1		c.-415C>T		5_prime_UTR_premature_start_codon_gain	Exon 6 of 11	ENSP00000496907.1	A0A3B3IRM1

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5917 AN: 152168 Hom.: 169 Cov.: 33

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0366

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0392

GnomAD2 exomes AF: 0.0372 AC: 9299 AN: 250084 AF XY: 0.0375

Gnomad AFR exome AF: 0.00905

Gnomad AMR exome AF: 0.0241

Gnomad ASJ exome AF: 0.0291

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0398

Gnomad NFE exome AF: 0.0585

Gnomad OTH exome AF: 0.0419

GnomAD4 exome AF: 0.0531 AC: 77599 AN: 1461470 Hom.: 2375 Cov.: 32 AF XY: 0.0518 AC XY: 37676 AN XY: 727052

African (AFR) AF: 0.00878 AC: 294 AN: 33476

American (AMR) AF: 0.0259 AC: 1157 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 729 AN: 26132

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.0103 AC: 892 AN: 86252

European-Finnish (FIN) AF: 0.0399 AC: 2130 AN: 53364

Middle Eastern (MID) AF: 0.0279 AC: 161 AN: 5768

European-Non Finnish (NFE) AF: 0.0623 AC: 69269 AN: 1111676

Other (OTH) AF: 0.0491 AC: 2962 AN: 60382

GnomAD4 genome AF: 0.0388 AC: 5914 AN: 152286 Hom.: 169 Cov.: 33 AF XY: 0.0368 AC XY: 2741 AN XY: 74460

African (AFR) AF: 0.0109 AC: 454 AN: 41562

American (AMR) AF: 0.0386 AC: 590 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0291 AC: 101 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4830

European-Finnish (FIN) AF: 0.0366 AC: 389 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0609 AC: 4144 AN: 68018

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0519 Hom.: 256

Bravo AF: 0.0391

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.0629

EpiControl AF: 0.0609

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.91
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs33970119; hg19: chr17-4804902;