20-35280684-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002212.4(EIF6):c.339C>T(p.Tyr113=) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.780

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]

ACMG classification

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 GnomAd at 464 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF6	NM_002212.4	c.339C>T	p.Tyr113=	synonymous_variant	4/7	ENST00000374450.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF6	ENST00000374450.8	c.339C>T	p.Tyr113=	synonymous_variant	4/7	1	NM_002212.4	P1

Frequencies

GnomAD3 genomes AF: 0.00305 AC: 464 AN: 152192 Hom.: 5 Cov.: 32

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.: 8 AF XY: 0.00383 AC XY: 518 AN XY: 135206

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.: 30 Cov.: 31 AF XY: 0.00414 AC XY: 3006 AN XY: 726886

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.: 5 Cov.: 32 AF XY: 0.00307 AC XY: 229 AN XY: 74484

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.: 1

Bravo AF: 0.00315

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.00632

EpiControl AF: 0.00581

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs138400954; hg19: chr20-33868487; COSMIC: COSV55770374; COSMIC: COSV55770374;