rs10505283

Variant names:

• chr8-116669336-C-T
• rs10505283
• NM_003756.3:c.290-10356G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003756.3(EIF3H):​c.290-10356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 152,212 control chromosomes in the GnomAD database, including 265 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 0.045 (265 hom., cov: 32)
• Consequence: EIF3H NM_003756.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537
• Publications: 3 publications found

Genes affected

EIF3H (HGNC:3273): (eukaryotic translation initiation factor 3 subunit H) Enables deubiquitinase activity. Contributes to translation initiation factor activity. Involved in negative regulation of proteasomal ubiquitin-dependent protein catabolic process and translational initiation. Located in extracellular exosome and membrane. Part of eukaryotic translation initiation factor 3 complex. Implicated in breast cancer; prostate cancer; and prostate carcinoma. Biomarker of prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3H	NM_003756.3	c.290-10356G>A		intron_variant	Intron 2 of 7	ENST00000521861.6	NP_003747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3H	ENST00000521861.6	c.290-10356G>A		intron_variant	Intron 2 of 7	1	NM_003756.3	ENSP00000429931.1

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6857 AN: 152094 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0533

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0255

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0446

Gnomad OTH AF: 0.0574

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

GnomAD4 genome AF: 0.0451 AC: 6868 AN: 152212 Hom.: 265 Cov.: 32 AF XY: 0.0462 AC XY: 3440 AN XY: 74428

African (AFR) AF: 0.0111 AC: 461 AN: 41544

American (AMR) AF: 0.145 AC: 2223 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3466

East Asian (EAS) AF: 0.0534 AC: 277 AN: 5184

South Asian (SAS) AF: 0.0610 AC: 294 AN: 4822

European-Finnish (FIN) AF: 0.0255 AC: 270 AN: 10596

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0446 AC: 3031 AN: 67998

Other (OTH) AF: 0.0610 AC: 129 AN: 2114

Alfa AF: 0.0455 Hom.: 267

Bravo AF: 0.0532

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Benign	0.64
PhyloP100		0.54
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: rs10505283; hg19: chr8-117681575;