Variant 22-36525714-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003753.4(EIF3D):c.124-5C>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 0.0026 in 1,609,918 control chromosomes in the GnomAD database, including 82 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 0.013 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 33 hom. )

Consequence

EIF3D
NM_003753.4 splice_region, intron

Scores

Splicing: ADA: 0.00007762

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.579

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:

EIF3D (HGNC:):

EIF3D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 22-36525714-G-A is Benign according to our data. Variant chr22-36525714-G-A is described in ClinVar as [Benign]. Clinvar id is 714839.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2054/152210) while in subpopulation AFR AF= 0.0464 (1928/41516). AF 95% confidence interval is 0.0447. There are 49 homozygotes in gnomad4. There are 962 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2054 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
EIF3D	NM_003753.4 linkuse as main transcript	c.124-5C>T	splice_region_variant, intron_variant	ENST00000216190.13	NP_003744.1	O15371-1
EIF3D	XM_047441560.1 linkuse as main transcript	c.124-5C>T	splice_region_variant, intron_variant		XP_047297516.1
EIF3D	NR_156418.2 linkuse as main transcript	n.225-5C>T	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF3D	ENST00000216190.13 linkuse as main transcript	c.124-5C>T		splice_region_variant, intron_variant		1	NM_003753.4	ENSP00000216190.8		O15371-1

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2026

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00531

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00910

GnomAD3 exomes

AF:

0.00383

AC:

940

AN:

245744

Hom.:

AF XY:

0.00277

AC XY:

368

AN XY:

132896

show subpopulations

Gnomad AFR exome

AF:

0.0489

Gnomad AMR exome

AF:

0.00286

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.000443

Gnomad SAS exome

AF:

0.000449

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000178

Gnomad OTH exome

AF:

0.00266

GnomAD4 exome

AF:

0.00146

AC:

2126

AN:

1457708

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

968

AN XY:

725138

show subpopulations

Gnomad4 AFR exome

AF:

0.0448

Gnomad4 AMR exome

AF:

0.00304

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.000541

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000176

Gnomad4 OTH exome

AF:

0.00392

GnomAD4 genome

AF:

0.0135

AC:

2054

AN:

152210

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

962

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0464

Gnomad4 AMR

AF:

0.00530

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00695

Hom.:

Bravo

AF:

0.0154

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

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

Labcorp Genetics (formerly Invitae), Labcorp

Aug 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

2.5

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000078

dbscSNV1_RF

Benign

0.0

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