8-116693979-T-C

Variant names:

• chr8-116693979-T-C
• rs12675038
• NM_003756.3:c.289+32037A>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.289+32037A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 150,542 control chromosomes in the GnomAD database, including 1,329 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 0.12 (1329 hom., cov: 32)
• Consequence: EIF3H NM_003756.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003756.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3H	NM_003756.3	MANE Select	c.289+32037A>G		intron	N/A	NP_003747.1	O15372

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3H	ENST00000521861.6	TSL:1 MANE Select	c.289+32037A>G		intron	N/A	ENSP00000429931.1	O15372
	EIF3H	ENST00000276682.8	TSL:2	c.331+32037A>G		intron	N/A	ENSP00000276682.4	B3KS98
	EIF3H	ENST00000966245.1		c.289+32037A>G		intron	N/A	ENSP00000636304.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17661 AN: 150426 Hom.: 1330 Cov.: 32

Gnomad AFR AF: 0.0824

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.0729

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.117 AC: 17674 AN: 150542 Hom.: 1329 Cov.: 32 AF XY: 0.118 AC XY: 8715 AN XY: 73628

African (AFR) AF: 0.0827 AC: 3306 AN: 39992

American (AMR) AF: 0.114 AC: 1730 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3454

East Asian (EAS) AF: 0.420 AC: 2173 AN: 5172

South Asian (SAS) AF: 0.0726 AC: 350 AN: 4824

European-Finnish (FIN) AF: 0.124 AC: 1314 AN: 10604

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.119 AC: 8069 AN: 67976

Other (OTH) AF: 0.107 AC: 224 AN: 2092

Alfa AF: 0.119 Hom.: 3090

Bravo AF: 0.117

Asia WGS AF: 0.212 AC: 736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.54
PhyloP100		0.16
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: rs12675038; hg19: chr8-117706218;