chr8-116715611-C-T

Position:

• chr8-116715611-C-T

Variant summary

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

The NM_003756.3(EIF3H):​c.289+10405G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,154 control chromosomes in the GnomAD database, including 60,407 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 0.89 (60407 hom., cov: 33)
• Consequence: EIF3H NM_003756.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF3H	NM_003756.3	c.289+10405G>A		intron_variant		ENST00000521861.6	NP_003747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF3H	ENST00000521861.6	c.289+10405G>A		intron_variant		1	NM_003756.3	ENSP00000429931	P1

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135148 AN: 152036 Hom.: 60359 Cov.: 33

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.892

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

GnomAD4 genome AF: 0.889 AC: 135245 AN: 152154 Hom.: 60407 Cov.: 33 AF XY: 0.884 AC XY: 65802 AN XY: 74402

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.886

Gnomad4 OTH AF: 0.893

Alfa AF: 0.877 Hom.: 9889

Bravo AF: 0.888

Asia WGS AF: 0.795 AC: 2763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.7
DANN	Benign	0.49

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: rs10505287; hg19: chr8-117727850;