rs201470386

Variant names:

• chr17-4901893-C-A
• rs201470386
• NM_001145536.2:c.*1360C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-4901893-C-A
• chr17-4901893-C-G
• chr17-4901893-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145536.2(C17orf107):​c.*1360C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,607,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: C17orf107 NM_001145536.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 0 publications found

Genes affected

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

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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
• congenital myasthenic syndrome 4B

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C17orf107	NM_001145536.2	c.*1360C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000381365.4	NP_001139008.1
CHRNE	NM_000080.4	c.500+39G>T		intron_variant	Intron 5 of 11	ENST00000649488.2	NP_000071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C17orf107	ENST00000381365.4	c.*1360C>A		3_prime_UTR_variant	Exon 3 of 3	2	NM_001145536.2	ENSP00000370770.3
CHRNE	ENST00000649488.2	c.500+39G>T		intron_variant	Intron 5 of 11		NM_000080.4	ENSP00000497829.1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151368 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000491

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000162 AC: 4 AN: 247416 AF XY: 0.0000149

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000901

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000158 AC: 23 AN: 1456124 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10 AN XY: 724624

African (AFR) AF: 0.000151 AC: 5 AN: 33180

American (AMR) AF: 0.0000224 AC: 1 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39628

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4818

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1108576

Other (OTH) AF: 0.0000333 AC: 2 AN: 60054

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151368 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73940

African (AFR) AF: 0.0000491 AC: 2 AN: 40704

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 12

Bravo AF: 0.0000416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.98
DANN	Benign	0.52
PhyloP100		0.055

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs201470386; hg19: chr17-4805188;