Genetic Variant EIF3D:c.711+7G>A (chr22-36519398-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Splicing: ADA: 0.00001646

Clinical Significance

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

Conservation

PhyloP100: -5.08

Publications

1 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003753.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3D	NM_003753.4	MANE Select	c.711+7G>A		splice_region intron	N/A	NP_003744.1	O15371-1
	EIF3D	NR_156418.2		n.812+7G>A		splice_region intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EIF3D	ENST00000216190.13	TSL:1 MANE Select	c.711+7G>A	splice_region intron	N/A	ENSP00000216190.8	O15371-1
EIF3D	ENST00000405442.5	TSL:5	c.711+7G>A	splice_region intron	N/A	ENSP00000385812.1	O15371-1
EIF3D	ENST00000886942.1		c.711+7G>A	splice_region intron	N/A	ENSP00000557001.1

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

3695

AN:

152092

Hom.:

138

Cov.:

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

GnomAD2 exomes

AF:

0.00638

AC:

1600

AN:

250916

AF XY:

0.00451

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 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.:

AF XY:

0.00217

AC XY:

1576

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0934

AC:

3127

AN:

33470

American (AMR)

AF:

0.00293

AC:

131

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00360

AC:

AN:

26126

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.000116

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000665

AC:

AN:

1111960

Other (OTH)

AF:

0.00439

AC:

265

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

171

342

514

685

856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.0243

AC:

3699

AN:

152210

Hom.:

138

Cov.:

AF XY:

0.0231

AC XY:

1716

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0857

AC:

3559

AN:

41518

American (AMR)

AF:

0.00628

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68012

Other (OTH)

AF:

0.0104

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

171

342

514

685

856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.00947

Hom.:

Bravo

AF:

0.0271

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.056

(source)

DANN

Benign

0.61

PhyloP100

-5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over