Variant 20-35280121-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002212.4(EIF6):c.370-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,613,118 control chromosomes in the GnomAD database, including 42,362 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5038 hom., cov: 31)

Exomes 𝑓: 0.22 ( 37324 hom. )

Consequence

EIF6
NM_002212.4 splice_region, intron

Scores

Splicing: ADA: 0.0001067

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.945

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF6	NM_002212.4 link	c.370-3C>T		splice_region_variant, intron_variant	Intron 4 of 6	ENST00000374450.8	NP_002203.1	P56537-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF6	ENST00000374450.8 link	c.370-3C>T		splice_region_variant, intron_variant	Intron 4 of 6	1	NM_002212.4	ENSP00000363574.3		P56537-1

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37767

AN:

151966

Hom.:

5021

Cov.:

show subpopulations

Gnomad AFR

AF:

0.339

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.213

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.229

GnomAD3 exomes

AF:

0.231

AC:

57941

AN:

250938

Hom.:

7447

AF XY:

0.237

AC XY:

32171

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.225

Gnomad SAS exome

AF:

0.356

Gnomad FIN exome

AF:

0.223

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.220

AC:

321567

AN:

1461032

Hom.:

37324

Cov.:

AF XY:

0.224

AC XY:

162845

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.347

Gnomad4 AMR exome

AF:

0.119

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.194

Gnomad4 SAS exome

AF:

0.356

Gnomad4 FIN exome

AF:

0.224

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.221

GnomAD4 genome

AF:

0.249

AC:

37823

AN:

152086

Hom.:

5038

Cov.:

AF XY:

0.249

AC XY:

18507

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.340

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.222

Gnomad4 EAS

AF:

0.212

Gnomad4 SAS

AF:

0.345

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.212

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.221

Hom.:

6733

Bravo

AF:

0.245

Asia WGS

AF:

0.316

AC:

1098

AN:

3478

EpiCase

AF:

0.211

EpiControl

AF:

0.216

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.8

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.070

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over