chr3-184319426-G-GGT

Variant names:

• chr3-184319426-G-GGT
• rs1168140244
• NM_198241.3:c.425-224_425-223dupGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_198241.3(EIF4G1):​c.425-224_425-223dupGT 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 0.020 (23 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.02 (2261/112920) while in subpopulation AMR AF= 0.0449 (495/11020). AF 95% confidence interval is 0.0416. There are 23 homozygotes in gnomad4. There are 1177 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2261 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4G1	NM_198241.3	c.425-224_425-223dupGT		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_425-262insGT		intron_variant	Intron 6 of 32	1	NM_198241.3	ENSP00000316879.5

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 2263 AN: 112830 Hom.: 23 Cov.: 0

Gnomad AFR AF: 0.00441

Gnomad AMI AF: 0.00268

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0237

Gnomad EAS AF: 0.0226

Gnomad SAS AF: 0.0202

Gnomad FIN AF: 0.0230

Gnomad MID AF: 0.0120

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0229

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

GnomAD4 genome AF: 0.0200 AC: 2261 AN: 112920 Hom.: 23 Cov.: 0 AF XY: 0.0217 AC XY: 1177 AN XY: 54144

Gnomad4 AFR AF: 0.00439

Gnomad4 AMR AF: 0.0449

Gnomad4 ASJ AF: 0.0237

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.0230

Gnomad4 NFE AF: 0.0222

Gnomad4 OTH AF: 0.0233

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;