22-36523400-C-T

Position:

• chr22-36523400-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55

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 -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	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF3D	NM_003753.4	c.393-119G>A		intron_variant		ENST00000216190.13
EIF3D	XM_047441560.1	c.393-119G>A		intron_variant
EIF3D	NR_156418.2	n.494-119G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF3D	ENST00000216190.13	c.393-119G>A		intron_variant		1	NM_003753.4	P1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60795 AN: 151956 Hom.: 16681 Cov.: 32

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

Gnomad4 AFR exome AF: 0.803

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.207

Gnomad4 SAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.400 AC: 60892 AN: 152074 Hom.: 16727 Cov.: 32 AF XY: 0.396 AC XY: 29444 AN XY: 74348

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.348

Alfa AF: 0.309 Hom.: 2222

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
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs2076084; hg19: chr22-36919447; COSMIC: COSV53404796; COSMIC: COSV53404796;