chr8-116664174-T-C

Variant names:

• chr8-116664174-T-C
• rs10505281
• NM_003756.3:c.290-5194A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003756.3(EIF3H):​c.290-5194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 152,272 control chromosomes in the GnomAD database, including 88 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 0.026 (88 hom., cov: 32)
• Consequence: EIF3H NM_003756.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.859
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3H	NM_003756.3	c.290-5194A>G		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.290-5194A>G		intron_variant	Intron 2 of 7	1	NM_003756.3	ENSP00000429931.1

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3892 AN: 152154 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0144

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

GnomAD4 genome AF: 0.0256 AC: 3896 AN: 152272 Hom.: 88 Cov.: 32 AF XY: 0.0245 AC XY: 1823 AN XY: 74464

African (AFR) AF: 0.0658 AC: 2732 AN: 41546

American (AMR) AF: 0.0131 AC: 200 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4824

European-Finnish (FIN) AF: 0.0167 AC: 177 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0107 AC: 730 AN: 68014

Other (OTH) AF: 0.0142 AC: 30 AN: 2106

Alfa AF: 0.0157 Hom.: 28

Bravo AF: 0.0268

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		0.86
Mutation Taster		=100/0	polymorphism

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: rs10505281; hg19: chr8-117676413;