Genetic Variant EIF4A1:p.Ser89Ser (chr17-7575180-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001416.4(EIF4A1):c.267G>A(p.Ser89Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,612,794 control chromosomes in the GnomAD database, including 15,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1606 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13513 hom. )

Consequence

EIF4A1
NM_001416.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.192

Variant links:

Genes affected

EIF4A1 (HGNC:3282): (eukaryotic translation initiation factor 4A1) Enables double-stranded RNA binding activity. Predicted to be involved in cytoplasmic translational initiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

EIF4A1 links:

SENP3-EIF4A1 (HGNC:49182): (SENP3-EIF4A1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring SUMO1/sentrin/SMT3 specific peptidase 3 (SENP3) and eukaryotic translation initiation factor 4A1 (EIF4A1) genes on chromosome 17. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

SENP3-EIF4A1 links:

ENSG00000264772 (HGNC:):

ENSG00000264772 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 17-7575180-G-A is Benign according to our data. Variant chr17-7575180-G-A is described in ClinVar as [Benign]. Clinvar id is 1328715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.192 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4A1	NM_001416.4 link	c.267G>A	p.Ser89Ser	synonymous_variant	Exon 4 of 11	ENST00000293831.13	NP_001407.1	P60842-1
EIF4A1	NM_001204510.2 link	c.267G>A	p.Ser89Ser	synonymous_variant	Exon 4 of 11		NP_001191439.1	P60842-2
SENP3-EIF4A1	NR_037926.1 link	n.2829G>A		non_coding_transcript_exon_variant	Exon 15 of 22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EIF4A1	ENST00000293831.13 link	c.267G>A	p.Ser89Ser	synonymous_variant	Exon 4 of 11	1	NM_001416.4	ENSP00000293831.8	P60842-1
SENP3-EIF4A1	ENST00000614237.1 link	n.*713G>A		non_coding_transcript_exon_variant	Exon 14 of 21	2		ENSP00000483614.1	A0A087X0R7
SENP3-EIF4A1	ENST00000614237.1 link	n.*713G>A		3_prime_UTR_variant	Exon 14 of 21	2		ENSP00000483614.1	A0A087X0R7

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21187

AN:

151982

Hom.:

1600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.0933

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.117

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.132

AC:

33183

AN:

251430

Hom.:

2480

AF XY:

0.135

AC XY:

18309

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.0541

Gnomad ASJ exome

AF:

0.110

Gnomad EAS exome

AF:

0.123

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.173

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.134

AC:

195018

AN:

1460694

Hom.:

13513

Cov.:

AF XY:

0.135

AC XY:

97855

AN XY:

726670

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.0562

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.118

Gnomad4 SAS exome

AF:

0.176

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.139

AC:

21212

AN:

152100

Hom.:

1606

Cov.:

AF XY:

0.140

AC XY:

10420

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.164

Gnomad4 AMR

AF:

0.0932

Gnomad4 ASJ

AF:

0.106

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.136

Hom.:

675

Bravo

AF:

0.133

Asia WGS

AF:

0.169

AC:

587

AN:

3478

EpiCase

AF:

0.124

EpiControl

AF:

0.124

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 17, 2021

GeneDx

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

-0.51

CADD

Benign

4.1

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over