rs140756451

Variant names:

• chr17-4902351-G-A
• rs140756451
• NM_001145536.2:c.*1818G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-4902351-G-A
• chr17-4902351-G-C
• chr17-4902351-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001145536.2(C17orf107):​c.*1818G>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 0.000444 in 1,613,050 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: C17orf107 NM_001145536.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.07
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-4902351-G-A is Benign according to our data. Variant chr17-4902351-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 254895.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145536.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf107	NM_001145536.2	MANE Select	c.*1818G>A		3_prime_UTR	Exon 3 of 3	NP_001139008.1
	CHRNE	NM_000080.4	MANE Select	c.235-25C>T		intron	N/A	NP_000071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf107	ENST00000381365.4	TSL:2 MANE Select	c.*1818G>A		3_prime_UTR	Exon 3 of 3	ENSP00000370770.3
	CHRNE	ENST00000649488.2	MANE Select	c.235-25C>T		intron	N/A	ENSP00000497829.1
	CHRNE	ENST00000649830.1		c.-699-25C>T		intron	N/A	ENSP00000496907.1

Frequencies

GnomAD3 genomes AF: 0.00247 AC: 376 AN: 152186 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00849

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.000632 AC: 159 AN: 251482 AF XY: 0.000456

Gnomad AFR exome AF: 0.00874

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000233 AC: 341 AN: 1460746 Hom.: 0 Cov.: 35 AF XY: 0.000201 AC XY: 146 AN XY: 726788

African (AFR) AF: 0.00834 AC: 279 AN: 33460

American (AMR) AF: 0.000447 AC: 20 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1110972

Other (OTH) AF: 0.000464 AC: 28 AN: 60360

GnomAD4 genome AF: 0.00246 AC: 375 AN: 152304 Hom.: 2 Cov.: 32 AF XY: 0.00222 AC XY: 165 AN XY: 74468

African (AFR) AF: 0.00847 AC: 352 AN: 41572

American (AMR) AF: 0.000915 AC: 14 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

Other (OTH) AF: 0.00237 AC: 5 AN: 2108

Alfa AF: 0.000127 Hom.: 0

Bravo AF: 0.00282

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0060
DANN	Benign	0.65
PhyloP100		-5.1
Mutation Taster		=100/0	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: rs140756451; hg19: chr17-4805646;