Variant 22-36518920-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003753.4(EIF3D):c.712-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,613,416 control chromosomes in the GnomAD database, including 312 homozygotes. In-silico tool predicts a benign outcome for this variant. 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_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003673

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.647

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]

EIF3D links:

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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 22-36518920-G-A is Benign according to our data. Variant chr22-36518920-G-A is described in ClinVar as [Benign]. Clinvar id is 780650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
EIF3D	NM_003753.4 linkuse as main transcript	c.712-10C>T	splice_polypyrimidine_tract_variant, intron_variant	ENST00000216190.13
EIF3D	XM_047441560.1 linkuse as main transcript	c.712-10C>T	splice_polypyrimidine_tract_variant, intron_variant
EIF3D	NR_156418.2 linkuse as main transcript	n.813-10C>T	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
EIF3D	ENST00000216190.13 linkuse as main transcript	c.712-10C>T	splice_polypyrimidine_tract_variant, intron_variant	1	NM_003753.4	P1	O15371-1
EIF3D	ENST00000405442.5 linkuse as main transcript	c.712-10C>T	splice_polypyrimidine_tract_variant, intron_variant	5		P1	O15371-1
EIF3D	ENST00000455547.5 linkuse as main transcript	c.712-10C>T	splice_polypyrimidine_tract_variant, intron_variant	5
EIF3D	ENST00000458572.1 linkuse as main transcript	c.98-10C>T	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

3700

AN:

152162

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0860

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:

0.000147

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00635

AC:

1593

AN:

250760

Hom.:

AF XY:

0.00448

AC XY:

607

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.0891

Gnomad AMR exome

AF:

0.00290

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00254

AC:

3709

AN:

1461136

Hom.:

174

Cov.:

AF XY:

0.00217

AC XY:

1579

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.0938

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.00356

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000576

Gnomad4 OTH exome

AF:

0.00444

GnomAD4 genome

AF:

0.0243

AC:

3706

AN:

152280

Hom.:

138

Cov.:

AF XY:

0.0231

AC XY:

1719

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0859

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:

0.000147

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0182

Hom.:

Bravo

AF:

0.0272

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.0

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000037

dbscSNV1_RF

Benign

0.0020

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