chr17-4899489-G-A

Variant names:

• chr17-4899489-G-A
• rs1555546423
• NM_000080.4:c.1011C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000080.4(CHRNE):​c.1011C>T​(p.Ala337Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CHRNE NM_000080.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.77
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 17-4899489-G-A is Benign according to our data. Variant chr17-4899489-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 465848.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.77 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNE	NM_000080.4	c.1011C>T	p.Ala337Ala	synonymous_variant	Exon 9 of 12	ENST00000649488.2	NP_000071.1
C17orf107	NM_001145536.2	c.-274G>A		upstream_gene_variant		ENST00000381365.4	NP_001139008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNE	ENST00000649488.2	c.1011C>T	p.Ala337Ala	synonymous_variant	Exon 9 of 12		NM_000080.4	ENSP00000497829.1
C17orf107	ENST00000381365.4	c.-274G>A		upstream_gene_variant		2	NM_001145536.2	ENSP00000370770.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448306 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 718928

African (AFR) AF: 0.00 AC: 0 AN: 33352

American (AMR) AF: 0.00 AC: 0 AN: 42918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 39264

South Asian (SAS) AF: 0.00 AC: 0 AN: 83574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5528

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107042

Other (OTH) AF: 0.00 AC: 0 AN: 59870

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital myasthenic syndrome 4A Benign:1

Nov 22, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.8
DANN	Benign	0.80
PhyloP100		2.8
PromoterAI		-0.041	Neutral

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: rs1555546423; hg19: chr17-4802784;