20-35280121-G-A

Variant summary

Our verdict is Benign. The variant received -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

2
Splicing: ADA: 0.0001067
2

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]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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
EIF6NM_002212.4 linkc.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
EIF6ENST00000374450.8 linkc.370-3C>T splice_region_variant, intron_variant Intron 4 of 6 1 NM_002212.4 ENSP00000363574.3 P56537-1
ENSG00000261582ENST00000444717.1 linkn.-78C>T upstream_gene_variant 3 ENSP00000489186.1 A0A0U1RQV5

Frequencies

GnomAD3 genomes
AF:
0.249
AC:
37767
AN:
151966
Hom.:
5021
Cov.:
31
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
GnomAD2 exomes
AF:
0.231
AC:
57941
AN:
250938
AF XY:
0.237
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 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.:
36
AF XY:
0.224
AC XY:
162845
AN XY:
726838
show subpopulations
Gnomad4 AFR exome
AF:
0.347
AC:
11627
AN:
33464
Gnomad4 AMR exome
AF:
0.119
AC:
5312
AN:
44690
Gnomad4 ASJ exome
AF:
0.224
AC:
5834
AN:
26098
Gnomad4 EAS exome
AF:
0.194
AC:
7713
AN:
39694
Gnomad4 SAS exome
AF:
0.356
AC:
30737
AN:
86222
Gnomad4 FIN exome
AF:
0.224
AC:
11966
AN:
53392
Gnomad4 NFE exome
AF:
0.210
AC:
233789
AN:
1111340
Gnomad4 Remaining exome
AF:
0.221
AC:
13372
AN:
60372
Heterozygous variant carriers
0
11712
23425
35137
46850
58562
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
8148
16296
24444
32592
40740
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.249
AC:
37823
AN:
152086
Hom.:
5038
Cov.:
31
AF XY:
0.249
AC XY:
18507
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.340
AC:
0.33998
AN:
0.33998
Gnomad4 AMR
AF:
0.170
AC:
0.17033
AN:
0.17033
Gnomad4 ASJ
AF:
0.222
AC:
0.22235
AN:
0.22235
Gnomad4 EAS
AF:
0.212
AC:
0.21191
AN:
0.21191
Gnomad4 SAS
AF:
0.345
AC:
0.345292
AN:
0.345292
Gnomad4 FIN
AF:
0.227
AC:
0.226611
AN:
0.226611
Gnomad4 NFE
AF:
0.212
AC:
0.212327
AN:
0.212327
Gnomad4 OTH
AF:
0.231
AC:
0.231025
AN:
0.231025
Heterozygous variant carriers
0
1425
2850
4276
5701
7126
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
414
828
1242
1656
2070
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.225
Hom.:
13638
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
Mutation Taster
=100/0
polymorphism (auto)

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.

Other links and lift over

dbSNP: rs2250205; hg19: chr20-33867924; COSMIC: COSV55768447; COSMIC: COSV55768447; API