22-36519398-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003753.4(EIF3D):​c.711+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,614,004 control chromosomes in the GnomAD database, including 312 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 138 hom., cov: 32)
Exomes 𝑓: 0.0025 ( 174 hom. )

Consequence

EIF3D
NM_003753.4 splice_region, intron

Scores

2
Splicing: ADA: 0.00001646
2

Clinical Significance

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

Conservation

PhyloP100: -5.08
Variant links:
Genes affected
EIF3D (HGNC:3278): (eukaryotic translation initiation factor 3 subunit D) Eukaryotic translation initiation factor-3 (eIF3), the largest of the eIFs, is a multiprotein complex composed of at least ten nonidentical subunits. The complex binds to the 40S ribosome and helps maintain the 40S and 60S ribosomal subunits in a dissociated state. It is also thought to play a role in the formation of the 40S initiation complex by interacting with the ternary complex of eIF2/GTP/methionyl-tRNA, and by promoting mRNA binding. The protein encoded by this gene is the major RNA binding subunit of the eIF3 complex. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 22-36519398-C-T is Benign according to our data. Variant chr22-36519398-C-T is described in ClinVar as [Benign]. Clinvar id is 780651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EIF3DNM_003753.4 linkc.711+7G>A splice_region_variant, intron_variant Intron 8 of 14 ENST00000216190.13 NP_003744.1 O15371-1
EIF3DXM_047441560.1 linkc.711+7G>A splice_region_variant, intron_variant Intron 8 of 9 XP_047297516.1
EIF3DNR_156418.2 linkn.812+7G>A splice_region_variant, intron_variant Intron 8 of 14

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EIF3DENST00000216190.13 linkc.711+7G>A splice_region_variant, intron_variant Intron 8 of 14 1 NM_003753.4 ENSP00000216190.8 O15371-1
EIF3DENST00000405442.5 linkc.711+7G>A splice_region_variant, intron_variant Intron 8 of 14 5 ENSP00000385812.1 O15371-1
EIF3DENST00000455547.5 linkc.711+7G>A splice_region_variant, intron_variant Intron 9 of 9 5 ENSP00000390438.1 B0QYA5
EIF3DENST00000458572.1 linkn.96+7G>A splice_region_variant, intron_variant Intron 1 of 6 3 ENSP00000391061.2 B0QYA4

Frequencies

GnomAD3 genomes
AF:
0.0243
AC:
3695
AN:
152092
Hom.:
138
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0859
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00628
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00638
AC:
1600
AN:
250916
Hom.:
78
AF XY:
0.00451
AC XY:
611
AN XY:
135588
show subpopulations
Gnomad AFR exome
AF:
0.0893
Gnomad AMR exome
AF:
0.00286
Gnomad ASJ exome
AF:
0.00259
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000441
Gnomad OTH exome
AF:
0.00245
GnomAD4 exome
AF:
0.00254
AC:
3709
AN:
1461794
Hom.:
174
Cov.:
31
AF XY:
0.00217
AC XY:
1576
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.0934
Gnomad4 AMR exome
AF:
0.00293
Gnomad4 ASJ exome
AF:
0.00360
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000665
Gnomad4 OTH exome
AF:
0.00439
GnomAD4 genome
AF:
0.0243
AC:
3699
AN:
152210
Hom.:
138
Cov.:
32
AF XY:
0.0231
AC XY:
1716
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.0857
Gnomad4 AMR
AF:
0.00628
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00704
Hom.:
45
Bravo
AF:
0.0271
Asia WGS
AF:
0.00433
AC:
16
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

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

- -

Mar 02, 2018
Labcorp Genetics (formerly Invitae), Labcorp
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
-0.80
CADD
Benign
0.056
DANN
Benign
0.61
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000016
dbscSNV1_RF
Benign
0.0020
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.

Other links and lift over

dbSNP: rs7287906; hg19: chr22-36915445; API