Variant 20-35280684-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002212.4(EIF6):c.339C>T(p.Tyr113Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 1,613,696 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 30 hom. )

Consequence

EIF6
NM_002212.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.780

Variant links:

Genes affected

EIF6 (HGNC:6159): (eukaryotic translation initiation factor 6) Hemidesmosomes are structures which link the basal lamina to the intermediate filament cytoskeleton. An important functional component of hemidesmosomes is the integrin beta-4 subunit (ITGB4), a protein containing two fibronectin type III domains. The protein encoded by this gene binds to the fibronectin type III domains of ITGB4 and may help link ITGB4 to the intermediate filament cytoskeleton. The encoded protein, which is insoluble and found both in the nucleus and in the cytoplasm, can function as a translation initiation factor and prevent the association of the 40S and 60S ribosomal subunits. Multiple non-protein coding transcript variants and variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

EIF6 links:

EIF6 (HGNC:):

EIF6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 20-35280684-G-A is Benign according to our data. Variant chr20-35280684-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3234142.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.78 with no splicing effect.

BS2

High AC in GnomAd4 at 463 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF6	NM_002212.4 linkuse as main transcript	c.339C>T	p.Tyr113Tyr	synonymous_variant	4/7	ENST00000374450.8	NP_002203.1	P56537-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF6	ENST00000374450.8 linkuse as main transcript	c.339C>T	p.Tyr113Tyr	synonymous_variant	4/7	1	NM_002212.4	ENSP00000363574.3		P56537-1

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

464

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00448

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00343

AC:

859

AN:

250176

Hom.:

AF XY:

0.00383

AC XY:

518

AN XY:

135206

show subpopulations

Gnomad AFR exome

AF:

0.000683

Gnomad AMR exome

AF:

0.00209

Gnomad ASJ exome

AF:

0.000597

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00975

Gnomad FIN exome

AF:

0.000418

Gnomad NFE exome

AF:

0.00387

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00385

AC:

5631

AN:

1461386

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

3006

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00213

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00943

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.00388

Gnomad4 OTH exome

AF:

0.00444

GnomAD4 genome

AF:

0.00304

AC:

463

AN:

152310

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

229

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00891

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00448

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00355

Hom.:

Bravo

AF:

0.00315

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00632

EpiControl

AF:

0.00581

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

EIF6: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.7

DANN

Benign

0.82

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

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