NM_003753.4:c.-11+1251A>G

Variant names:

• chr22-36527825-T-C
• rs9610529
• NM_003753.4:c.-11+1251A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ENSG00000302270 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EIF3D	NM_003753.4	c.-11+1251A>G		intron_variant	Intron 1 of 14	ENST00000216190.13	NP_003744.1
EIF3D	NR_156418.2	n.91+1251A>G		intron_variant	Intron 1 of 14
EIF3D	XM_047441560.1	c.-11+1251A>G		intron_variant	Intron 1 of 9		XP_047297516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3D	ENST00000216190.13	c.-11+1251A>G		intron_variant	Intron 1 of 14	1	NM_003753.4	ENSP00000216190.8

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

African (AFR) AF: 0.562 AC: 23295 AN: 41452

American (AMR) AF: 0.263 AC: 4021 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3470

East Asian (EAS) AF: 0.00734 AC: 38 AN: 5178

South Asian (SAS) AF: 0.118 AC: 569 AN: 4822

European-Finnish (FIN) AF: 0.186 AC: 1961 AN: 10564

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15375 AN: 67980

Other (OTH) AF: 0.245 AC: 517 AN: 2108

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
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9610529; hg19: chr22-36923872;