22-36519398-C-T

Variant names:

• chr22-36519398-C-T
• rs7287906
• NM_003753.4:c.711+7G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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

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]

ACMG classification

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
EIF3D	NM_003753.4	c.711+7G>A		splice_region_variant, intron_variant	Intron 8 of 14	ENST00000216190.13	NP_003744.1
EIF3D	XM_047441560.1	c.711+7G>A		splice_region_variant, intron_variant	Intron 8 of 9		XP_047297516.1
EIF3D	NR_156418.2	n.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
EIF3D	ENST00000216190.13	c.711+7G>A		splice_region_variant, intron_variant	Intron 8 of 14	1	NM_003753.4	ENSP00000216190.8
EIF3D	ENST00000405442.5	c.711+7G>A		splice_region_variant, intron_variant	Intron 8 of 14	5		ENSP00000385812.1
EIF3D	ENST00000455547.5	c.711+7G>A		splice_region_variant, intron_variant	Intron 9 of 9	5		ENSP00000390438.1
EIF3D	ENST00000458572.1	n.96+7G>A		splice_region_variant, intron_variant	Intron 1 of 6	3		ENSP00000391061.2

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3695 AN: 152092 Hom.: 138 Cov.: 32

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

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

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

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

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

Other links and lift over

dbSNP: rs7287906; hg19: chr22-36915445;