NM_198241.3:c.425-222_425-207delTTGTGTGTGTGTGTGT

Variant names:

• chr3-184319451-GTGTGTGTGTGTGTGTT-G
• rs373186906
• NM_198241.3:c.425-222_425-207delTTGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_198241.3(EIF4G1):​c.425-222_425-207delTTGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (3543 hom., cov: 0)
• Consequence: EIF4G1 NM_198241.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.10
• 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 -10 ACMG points.

• BP6: Variant 3-184319451-GTGTGTGTGTGTGTGTT-G is Benign according to our data. Variant chr3-184319451-GTGTGTGTGTGTGTGTT-G is described in ClinVar as Benign. ClinVar VariationId is 1283267.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

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.425-222_425-207delTTGTGTGTGTGTGTGT		intron	N/A	NP_937884.2	Q04637-1
	EIF4G1	NM_001194946.2		c.446-222_446-207delTTGTGTGTGTGTGTGT		intron	N/A	NP_001181875.2	Q04637-9
	EIF4G1	NM_001194947.2		c.446-222_446-207delTTGTGTGTGTGTGTGT		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.425-237_425-222delTGTGTGTGTGTGTGTT		intron	N/A	ENSP00000316879.5	Q04637-1
	EIF4G1	ENST00000352767.7	TSL:1	c.446-237_446-222delTGTGTGTGTGTGTGTT		intron	N/A	ENSP00000338020.4	Q04637-9
	EIF4G1	ENST00000382330.7	TSL:1	c.446-237_446-222delTGTGTGTGTGTGTGTT		intron	N/A	ENSP00000371767.3	Q04637-9

Frequencies

GnomAD3 genomes AF: 0.294 AC: 31023 AN: 105360 Hom.: 3544 Cov.: 0

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.0923

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.295 AC: 31046 AN: 105416 Hom.: 3543 Cov.: 0 AF XY: 0.288 AC XY: 14750 AN XY: 51140

African (AFR) AF: 0.460 AC: 10389 AN: 22588

American (AMR) AF: 0.235 AC: 2495 AN: 10610

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 661 AN: 2474

East Asian (EAS) AF: 0.0921 AC: 341 AN: 3702

South Asian (SAS) AF: 0.259 AC: 912 AN: 3522

European-Finnish (FIN) AF: 0.233 AC: 1713 AN: 7366

Middle Eastern (MID) AF: 0.304 AC: 62 AN: 204

European-Non Finnish (NFE) AF: 0.263 AC: 13907 AN: 52936

Other (OTH) AF: 0.305 AC: 425 AN: 1394

Alfa AF: 0.187 Hom.: 13

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs373186906; hg19: chr3-184037239;