chr3-184319426-GGTGT-G

Variant names:

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

Variant summary

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

The NM_198241.3(EIF4G1):​c.425-226_425-223delGTGT 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 0.0059 (5 hom., cov: 0)
• Consequence: EIF4G1 NM_198241.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74

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 eas. gnomad4 allele frequency = 0.00588 (664/112952) while in subpopulation EAS AF= 0.0475 (195/4102). AF 95% confidence interval is 0.0421. There are 5 homozygotes in gnomad4. There are 354 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 664 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4G1	NM_198241.3	c.425-226_425-223delGTGT		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.425-262_425-259delGTGT		intron_variant	Intron 6 of 32	1	NM_198241.3	ENSP00000316879.5

Frequencies

GnomAD3 genomes AF: 0.00586 AC: 661 AN: 112862 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.00115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00414

Gnomad EAS AF: 0.0474

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.00299

Gnomad MID AF: 0.00800

Gnomad NFE AF: 0.00385

Gnomad OTH AF: 0.00858

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

GnomAD4 genome AF: 0.00588 AC: 664 AN: 112952 Hom.: 5 Cov.: 0 AF XY: 0.00654 AC XY: 354 AN XY: 54160

Gnomad4 AFR AF: 0.00114

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.00414

Gnomad4 EAS AF: 0.0475

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.00299

Gnomad4 NFE AF: 0.00385

Gnomad4 OTH AF: 0.00990

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;