3-184319426-GGTGTGTGTGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGTGTGT

Variant names:

• chr3-184319426-GGTGTGT-G
• rs1168140244
• NM_198241.3:c.425-228_425-223delGTGTGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_198241.3(EIF4G1):​c.425-228_425-223delGTGTGT 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 0.0017 (3 hom., cov: 0)
• Consequence: EIF4G1 NM_198241.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00174 (196/112962) while in subpopulation EAS AF = 0.0268 (110/4106). AF 95% confidence interval is 0.0227. There are 3 homozygotes in GnomAd4. There are 107 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 196 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.425-228_425-223delGTGTGT		intron	N/A	NP_937884.2	Q04637-1
	EIF4G1	NM_001194946.2		c.446-228_446-223delGTGTGT		intron	N/A	NP_001181875.2	Q04637-9
	EIF4G1	NM_001194947.2		c.446-228_446-223delGTGTGT		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.425-262_425-257delGTGTGT		intron	N/A	ENSP00000316879.5	Q04637-1
	EIF4G1	ENST00000352767.7	TSL:1	c.446-262_446-257delGTGTGT		intron	N/A	ENSP00000338020.4	Q04637-9
	EIF4G1	ENST00000382330.7	TSL:1	c.446-262_446-257delGTGTGT		intron	N/A	ENSP00000371767.3	Q04637-9

Frequencies

GnomAD3 genomes AF: 0.00170 AC: 192 AN: 112872 Hom.: 3 Cov.: 0

Gnomad AFR AF: 0.000148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000273

Gnomad ASJ AF: 0.00113

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.00491

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000984

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00174 AC: 196 AN: 112962 Hom.: 3 Cov.: 0 AF XY: 0.00198 AC XY: 107 AN XY: 54164

African (AFR) AF: 0.000147 AC: 4 AN: 27122

American (AMR) AF: 0.000272 AC: 3 AN: 11024

Ashkenazi Jewish (ASJ) AF: 0.00113 AC: 3 AN: 2658

East Asian (EAS) AF: 0.0268 AC: 110 AN: 4106

South Asian (SAS) AF: 0.00492 AC: 17 AN: 3452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.000985 AC: 54 AN: 54846

Other (OTH) AF: 0.00354 AC: 5 AN: 1414

Alfa AF: 0.00 Hom.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

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;