chr3-184315838-A-C

Position:

• chr3-184315838-A-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_198241.3(EIF4G1):​c.42A>C​(p.Pro14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000050 (0 hom., cov: 32)
  • Exomes 𝑓: 0.024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EIF4G1 NM_198241.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.358

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 3-184315838-A-C is Benign according to our data. Variant chr3-184315838-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3049318.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.358 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF4G1	NM_198241.3	c.42A>C	p.Pro14=	synonymous_variant	3/33	ENST00000346169.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF4G1	ENST00000346169.7	c.42A>C	p.Pro14=	synonymous_variant	3/33	1	NM_198241.3	A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 7 AN: 140640 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.0000254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000303

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000264

Gnomad FIN AF: 0.000343

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000156

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0237 AC: 10458 AN: 440508 Hom.: 0 Cov.: 13 AF XY: 0.0201 AC XY: 4776 AN XY: 237086

Gnomad4 AFR exome AF: 0.0152

Gnomad4 AMR exome AF: 0.000426

Gnomad4 ASJ exome AF: 0.00566

Gnomad4 EAS exome AF: 0.00264

Gnomad4 SAS exome AF: 0.00345

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0364

Gnomad4 OTH exome AF: 0.0187

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000497 AC: 7 AN: 140762 Hom.: 0 Cov.: 32 AF XY: 0.0000293 AC XY: 2 AN XY: 68280

Gnomad4 AFR AF: 0.0000254

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000303

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000263

Gnomad4 FIN AF: 0.000343

Gnomad4 NFE AF: 0.0000156

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

EIF4G1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8

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: rs1722671223; hg19: chr3-184033626;