8-38057220-G-A

Variant names:

• chr8-38057220-G-A
• rs61753671
• NM_004095.4:c.285G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004095.4(EIF4EBP1):​c.285G>A​(p.Gln95Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,614,060 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (10 hom., cov: 34)
  • Exomes 𝑓: 0.013 (147 hom.)
• Consequence: EIF4EBP1 NM_004095.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.212

Genes affected

EIF4EBP1 (HGNC:3288): (eukaryotic translation initiation factor 4E binding protein 1) This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from eIF4E and activation of mRNA translation. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 8-38057220-G-A is Benign according to our data. Variant chr8-38057220-G-A is described in ClinVar as [Benign]. Clinvar id is 774460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.212 with no splicing effect.
• BS2: High AC in GnomAd4 at 1417 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4EBP1	NM_004095.4	c.285G>A	p.Gln95Gln	synonymous_variant	Exon 2 of 3	ENST00000338825.5	NP_004086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4EBP1	ENST00000338825.5	c.285G>A	p.Gln95Gln	synonymous_variant	Exon 2 of 3	1	NM_004095.4	ENSP00000340691.4
EIF4EBP1	ENST00000520657.1	n.193G>A		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.00931 AC: 1417 AN: 152212 Hom.: 10 Cov.: 34

Gnomad AFR AF: 0.00289

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.00442

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00940 AC: 2359 AN: 250876 AF XY: 0.00931

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00616

Gnomad ASJ exome AF: 0.0308

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00231

Gnomad NFE exome AF: 0.0136

Gnomad OTH exome AF: 0.0132

GnomAD4 exome AF: 0.0129 AC: 18802 AN: 1461730 Hom.: 147 Cov.: 32 AF XY: 0.0124 AC XY: 9045 AN XY: 727162

Gnomad4 AFR exome AF: 0.00164 AC: 55 AN: 33478

Gnomad4 AMR exome AF: 0.00637 AC: 285 AN: 44714

Gnomad4 ASJ exome AF: 0.0317 AC: 829 AN: 26120

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39696

Gnomad4 SAS exome AF: 0.00479 AC: 413 AN: 86248

Gnomad4 FIN exome AF: 0.00286 AC: 153 AN: 53408

Gnomad4 NFE exome AF: 0.0145 AC: 16092 AN: 1111912

Gnomad4 Remaining exome AF: 0.0149 AC: 900 AN: 60386

GnomAD4 genome AF: 0.00930 AC: 1417 AN: 152330 Hom.: 10 Cov.: 34 AF XY: 0.00913 AC XY: 680 AN XY: 74490

Gnomad4 AFR AF: 0.00289 AC: 0.00288628 AN: 0.00288628

Gnomad4 AMR AF: 0.00810 AC: 0.00810246 AN: 0.00810246

Gnomad4 ASJ AF: 0.0329 AC: 0.032872 AN: 0.032872

Gnomad4 EAS AF: 0.000193 AC: 0.000192901 AN: 0.000192901

Gnomad4 SAS AF: 0.00662 AC: 0.00662252 AN: 0.00662252

Gnomad4 FIN AF: 0.00442 AC: 0.00442395 AN: 0.00442395

Gnomad4 NFE AF: 0.0137 AC: 0.013746 AN: 0.013746

Gnomad4 OTH AF: 0.00803 AC: 0.00803403 AN: 0.00803403

Alfa AF: 0.0132 Hom.: 7

Asia WGS AF: 0.00433 AC: 16 AN: 3478

EpiCase AF: 0.0158

EpiControl AF: 0.0141

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.7
DANN	Benign	0.52
Mutation Taster		=100/0	polymorphism

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: rs61753671; hg19: chr8-37914738; COSMIC: COSV100125935;