chr3-184319449-GTGTGTGTGTGTGTGTGTT-G

Position:

• chr3-184319449-GTGTGTGTGTGTGTGTGTT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_198241.3(EIF4G1):​c.425-221_425-204del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.075 (257 hom., cov: 0)
• Consequence: EIF4G1 NM_198241.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.10

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 -10 ACMG points.

• BP6: Variant 3-184319449-GTGTGTGTGTGTGTGTGTT-G is Benign according to our data. Variant chr3-184319449-GTGTGTGTGTGTGTGTGTT-G is described in ClinVar as [Benign]. Clinvar id is 1280193.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4G1	NM_198241.3	c.425-221_425-204del		intron_variant		ENST00000346169.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4G1	ENST00000346169.7	c.425-221_425-204del		intron_variant		1	NM_198241.3	A2

Frequencies

GnomAD3 genomes AF: 0.0748 AC: 6277 AN: 83874 Hom.: 259 Cov.: 0

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.0177

Gnomad SAS AF: 0.0466

Gnomad FIN AF: 0.0230

Gnomad MID AF: 0.0592

Gnomad NFE AF: 0.0353

Gnomad OTH AF: 0.0744

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

GnomAD4 genome AF: 0.0749 AC: 6282 AN: 83906 Hom.: 257 Cov.: 0 AF XY: 0.0730 AC XY: 2972 AN XY: 40732

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.0504

Gnomad4 ASJ AF: 0.0282

Gnomad4 EAS AF: 0.0175

Gnomad4 SAS AF: 0.0468

Gnomad4 FIN AF: 0.0230

Gnomad4 NFE AF: 0.0354

Gnomad4 OTH AF: 0.0729

Alfa AF: 0.0340 Hom.: 1

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

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: rs775982504; hg19: chr3-184037237;