rs2302315

Variant names:

• chr17-4903133-G-A
• rs2302315
• ENST00000649830.1:c.-887-370C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000649830.1(CHRNE):​c.-887-370C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 1,511,588 control chromosomes in the GnomAD database, including 6,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (723 hom., cov: 31)
  • Exomes 𝑓: 0.089 (5657 hom.)
• Consequence: CHRNE ENST00000649830.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.756
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 17-4903133-G-A is Benign according to our data. Variant chr17-4903133-G-A is described in ClinVar as Benign. ClinVar VariationId is 254887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNE	NM_000080.4	c.-70C>T		upstream_gene_variant		ENST00000649488.2	NP_000071.1
C17orf107	NM_001145536.2	c.*2600G>A		downstream_gene_variant		ENST00000381365.4	NP_001139008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNE	ENST00000649830.1	c.-887-370C>T		intron_variant	Intron 1 of 10			ENSP00000496907.1
CHRNE	ENST00000649488.2	c.-70C>T		upstream_gene_variant			NM_000080.4	ENSP00000497829.1
C17orf107	ENST00000381365.4	c.*2600G>A		downstream_gene_variant		2	NM_001145536.2	ENSP00000370770.3

Frequencies

GnomAD3 genomes AF: 0.0967 AC: 14706 AN: 152024 Hom.: 723 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0670

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.0675

GnomAD4 exome AF: 0.0890 AC: 120972 AN: 1359446 Hom.: 5657 AF XY: 0.0871 AC XY: 59278 AN XY: 680770

African (AFR) AF: 0.124 AC: 3844 AN: 31050

American (AMR) AF: 0.0526 AC: 2285 AN: 43420

Ashkenazi Jewish (ASJ) AF: 0.0610 AC: 1542 AN: 25280

East Asian (EAS) AF: 0.0728 AC: 2817 AN: 38704

South Asian (SAS) AF: 0.0307 AC: 2550 AN: 83128

European-Finnish (FIN) AF: 0.135 AC: 7084 AN: 52326

Middle Eastern (MID) AF: 0.0677 AC: 374 AN: 5528

European-Non Finnish (NFE) AF: 0.0937 AC: 95878 AN: 1023222

Other (OTH) AF: 0.0810 AC: 4598 AN: 56788

GnomAD4 genome AF: 0.0967 AC: 14705 AN: 152142 Hom.: 723 Cov.: 31 AF XY: 0.0972 AC XY: 7231 AN XY: 74382

African (AFR) AF: 0.116 AC: 4810 AN: 41506

American (AMR) AF: 0.0669 AC: 1023 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 235 AN: 3470

East Asian (EAS) AF: 0.0498 AC: 257 AN: 5162

South Asian (SAS) AF: 0.0359 AC: 173 AN: 4822

European-Finnish (FIN) AF: 0.145 AC: 1533 AN: 10596

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0942 AC: 6405 AN: 67972

Other (OTH) AF: 0.0663 AC: 140 AN: 2112

Alfa AF: 0.0964 Hom.: 85

Bravo AF: 0.0901

Asia WGS AF: 0.0440 AC: 153 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.87
PhyloP100		0.76
PromoterAI		-0.046	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2302315; hg19: chr17-4806428; COSMIC: COSV53419433;