3-184319426-GGTGTGTGTGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr3-184319426-G-GGTGT
• rs1168140244
• NM_198241.3:c.425-226_425-223dupGTGT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_198241.3(EIF4G1):​c.425-226_425-223dupGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0066 (2 hom., cov: 0)
• Consequence: EIF4G1 NM_198241.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764
• Publications: 0 publications found

Genes affected

EIF4G1 (HGNC:3296): (eukaryotic translation initiation factor 4 gamma 1) The protein encoded by this gene is a component of the multi-subunit protein complex EIF4F. This complex facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. The recognition of the mRNA cap and the ATP-dependent unwinding of 5'-terminal secondary structure is catalyzed by factors in this complex. The subunit encoded by this gene is a large scaffolding protein that contains binding sites for other members of the EIF4F complex. A domain at its N-terminus can also interact with the poly(A)-binding protein, which may mediate the circularization of mRNA during translation. Alternative splicing results in multiple transcript variants, some of which are derived from alternative promoter usage. [provided by RefSeq, Aug 2010]

EIF4G1 Gene-Disease associations (from GenCC):

• Parkinson disease 18, autosomal dominant, susceptibility to

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 743 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198241.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4G1	NM_198241.3	MANE Select	c.425-226_425-223dupGTGT		intron	N/A	NP_937884.2	Q04637-1
	EIF4G1	NM_001194946.2		c.446-226_446-223dupGTGT		intron	N/A	NP_001181875.2	Q04637-9
	EIF4G1	NM_001194947.2		c.446-226_446-223dupGTGT		intron	N/A	NP_001181876.2	Q04637-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4G1	ENST00000346169.7	TSL:1 MANE Select	c.425-263_425-262insGTGT		intron	N/A	ENSP00000316879.5	Q04637-1
	EIF4G1	ENST00000352767.7	TSL:1	c.446-263_446-262insGTGT		intron	N/A	ENSP00000338020.4	Q04637-9
	EIF4G1	ENST00000382330.7	TSL:1	c.446-263_446-262insGTGT		intron	N/A	ENSP00000371767.3	Q04637-9

Frequencies

GnomAD3 genomes AF: 0.00658 AC: 743 AN: 112860 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00845

Gnomad ASJ AF: 0.000752

Gnomad EAS AF: 0.00802

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.00400

Gnomad NFE AF: 0.00740

Gnomad OTH AF: 0.00858

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00658 AC: 743 AN: 112950 Hom.: 2 Cov.: 0 AF XY: 0.00713 AC XY: 386 AN XY: 54158

African (AFR) AF: 0.00147 AC: 40 AN: 27120

American (AMR) AF: 0.00844 AC: 93 AN: 11024

Ashkenazi Jewish (ASJ) AF: 0.000752 AC: 2 AN: 2658

East Asian (EAS) AF: 0.00804 AC: 33 AN: 4104

South Asian (SAS) AF: 0.0104 AC: 36 AN: 3450

European-Finnish (FIN) AF: 0.0163 AC: 120 AN: 7356

Middle Eastern (MID) AF: 0.00427 AC: 1 AN: 234

European-Non Finnish (NFE) AF: 0.00740 AC: 406 AN: 54844

Other (OTH) AF: 0.00849 AC: 12 AN: 1414

Alfa AF: 0.00246 Hom.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.76
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: rs1168140244; hg19: chr3-184037214;