rs9610529

chr22-36527825-T-Cchr22-36527825-T-G

Variant summary

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

The NM_003753.4(EIF3D):c.-11+1251A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,060 control chromosomes in the GnomAD database, including 9,150 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 0.31 (9150 hom., cov: 32)
• Consequence: EIF3D NM_003753.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF3D	NM_003753.4	c.-11+1251A>G		intron_variant		ENST00000216190.13
EIF3D	XM_047441560.1	c.-11+1251A>G		intron_variant
EIF3D	NR_156418.2	n.91+1251A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF3D	ENST00000216190.13	c.-11+1251A>G		intron_variant		1	NM_003753.4	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46540 AN: 151942 Hom.: 9122 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.00732

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.248

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.307 AC: 46620 AN: 152060 Hom.: 9150 Cov.: 32 AF XY: 0.298 AC XY: 22186 AN XY: 74336

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.00734

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.245

Alfa AF: 0.191 Hom.: 607

Bravo AF: 0.326

Asia WGS AF: 0.0980 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.4
Dann	Benign	0.59

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: rs9610529; hg19: chr22-36923872;