rs3826784

chr19-10116334-A-Gchr19-10116334-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003755.5(EIF3G):c.596-260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 559,972 control chromosomes in the GnomAD database, including 102,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.59 (26383 hom., cov: 32)
  • Exomes 𝑓: 0.61 (76421 hom.)
• Consequence: EIF3G NM_003755.5 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -3.00

Genes affected

EIF3G (HGNC:3274): (eukaryotic translation initiation factor 3 subunit G) This gene encodes a core subunit of the eukaryotic translation initiation factor 3 (eIF3) complex, which is required for initiation of protein translation. An N-terminal caspase cleavage product of the encoded protein may stimulate degradation of DNA. A mutation in this gene is associated with narcolepsy. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF3G	NM_003755.5	c.596-260T>C		intron_variant		ENST00000253108.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF3G	ENST00000253108.9	c.596-260T>C		intron_variant		1	NM_003755.5	P1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88846 AN: 151898 Hom.: 26352 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.609 AC: 248506 AN: 407954 Hom.: 76421 Cov.: 3 AF XY: 0.613 AC XY: 131099 AN XY: 213728

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.688

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.715

Gnomad4 SAS exome AF: 0.682

Gnomad4 FIN exome AF: 0.614

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.601

GnomAD4 genome AF: 0.585 AC: 88935 AN: 152018 Hom.: 26383 Cov.: 32 AF XY: 0.591 AC XY: 43902 AN XY: 74308

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.614

Alfa AF: 0.574 Hom.: 5120

Bravo AF: 0.587

Asia WGS AF: 0.699 AC: 2428 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Cataplexy and narcolepsy Other:1

association, no assertion criteria provided

case-control

Center for Narcolepsy, Stanford University

Dec 10, 2014

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.092
Dann	Benign	0.076

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

Publications

LitVar

Other links and lift over

dbSNP: rs3826784; hg19: chr19-10227010;