Genetic Variant EIF3D:c.393-119G>A (chr22-36523400-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003753.4(EIF3D):c.393-119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 770,546 control chromosomes in the GnomAD database, including 41,788 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 16727 hom., cov: 32)

Exomes 𝑓: 0.26 ( 25061 hom. )

Consequence

EIF3D
NM_003753.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.55

Publications

4 publications found

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:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
EIF3D	NM_003753.4 link	c.393-119G>A	intron_variant	Intron 5 of 14	ENST00000216190.13	NP_003744.1
EIF3D	NR_156418.2 link	n.494-119G>A	intron_variant	Intron 5 of 14
EIF3D	XM_047441560.1 link	c.393-119G>A	intron_variant	Intron 5 of 9		XP_047297516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3D	ENST00000216190.13 link	c.393-119G>A		intron_variant	Intron 5 of 14	1	NM_003753.4	ENSP00000216190.8

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60795

AN:

151956

Hom.:

16681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.792

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.350

GnomAD4 exome

AF:

0.262

AC:

162105

AN:

618472

Hom.:

25061

AF XY:

0.266

AC XY:

86423

AN XY:

324716

show subpopulations

African (AFR)

AF:

0.803

AC:

12672

AN:

15774

American (AMR)

AF:

0.169

AC:

4594

AN:

27190

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

5234

AN:

14932

East Asian (EAS)

AF:

0.207

AC:

7268

AN:

35088

South Asian (SAS)

AF:

0.348

AC:

18084

AN:

51994

European-Finnish (FIN)

AF:

0.243

AC:

10239

AN:

42158

Middle Eastern (MID)

AF:

0.452

AC:

1714

AN:

3796

European-Non Finnish (NFE)

AF:

0.235

AC:

93089

AN:

396302

Other (OTH)

AF:

0.295

AC:

9211

AN:

31238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

5279

10558

15836

21115

26394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1606

3212

4818

6424

8030

<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:

0.400

AC:

60892

AN:

152074

Hom.:

16727

Cov.:

AF XY:

0.396

AC XY:

29444

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.792

AC:

32846

AN:

41472

American (AMR)

AF:

0.245

AC:

3738

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1210

AN:

3468

East Asian (EAS)

AF:

0.192

AC:

992

AN:

5176

South Asian (SAS)

AF:

0.329

AC:

1586

AN:

4814

European-Finnish (FIN)

AF:

0.242

AC:

2554

AN:

10574

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16793

AN:

67974

Other (OTH)

AF:

0.348

AC:

736

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1424

2849

4273

5698

7122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<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:

0.320

Hom.:

2462

Bravo

AF:

0.414

Asia WGS

AF:

0.306

AC:

1066

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0030

(source)

DANN

Benign

0.64

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over