NM_198241.3:c.425-230_425-223dupGTGTGTGT

Variant names:

• chr3-184319426-G-GGTGTGTGT
• rs1168140244
• NM_198241.3:c.425-230_425-223dupGTGTGTGT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_198241.3(EIF4G1):​c.425-230_425-223dupGTGTGTGT 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 0.0041 (2 hom., cov: 0)
• Consequence: EIF4G1 NM_198241.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 466 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4G1	NM_198241.3	c.425-230_425-223dupGTGTGTGT		intron_variant	Intron 6 of 32	ENST00000346169.7	NP_937884.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4G1	ENST00000346169.7	c.425-263_425-262insGTGTGTGT		intron_variant	Intron 6 of 32	1	NM_198241.3	ENSP00000316879.5

Frequencies

GnomAD3 genomes AF: 0.00413 AC: 466 AN: 112866 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.000925

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00188

Gnomad EAS AF: 0.00219

Gnomad SAS AF: 0.00144

Gnomad FIN AF: 0.00149

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00593

Gnomad OTH AF: 0.000715

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

GnomAD4 genome AF: 0.00413 AC: 466 AN: 112956 Hom.: 2 Cov.: 0 AF XY: 0.00410 AC XY: 222 AN XY: 54162

Gnomad4 AFR AF: 0.000922

Gnomad4 AMR AF: 0.00771

Gnomad4 ASJ AF: 0.00188

Gnomad4 EAS AF: 0.00219

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00149

Gnomad4 NFE AF: 0.00593

Gnomad4 OTH AF: 0.000707

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1168140244; hg19: chr3-184037214;