chr10-119073163-A-T

Variant names:

• chr10-119073163-A-T
• rs1397618
• NM_003750.4:c.378-110T>A

Variant summary

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

The NM_003750.4(EIF3A):​c.378-110T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 1,057,278 control chromosomes in the GnomAD database, including 474,965 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 0.85 (57351 hom., cov: 33)
  • Exomes 𝑓: 0.96 (417614 hom.)
• Consequence: EIF3A NM_003750.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 10 publications found

Genes affected

EIF3A (HGNC:3271): (eukaryotic translation initiation factor 3 subunit A) Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in IRES-dependent viral translational initiation; formation of cytoplasmic translation initiation complex; and viral translational termination-reinitiation. Located in cytosol; nucleolus; and nucleoplasm. Part of eukaryotic translation initiation factor 3 complex. [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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3A	NM_003750.4	c.378-110T>A		intron_variant	Intron 3 of 21	ENST00000369144.8	NP_003741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3A	ENST00000369144.8	c.378-110T>A		intron_variant	Intron 3 of 21	1	NM_003750.4	ENSP00000358140.3

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128849 AN: 152126 Hom.: 57342 Cov.: 33

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.982

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.989

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.886

GnomAD4 exome AF: 0.958 AC: 867174 AN: 905036 Hom.: 417614 AF XY: 0.959 AC XY: 437331 AN XY: 455942

African (AFR) AF: 0.537 AC: 10946 AN: 20384

American (AMR) AF: 0.949 AC: 19911 AN: 20972

Ashkenazi Jewish (ASJ) AF: 0.981 AC: 16617 AN: 16936

East Asian (EAS) AF: 0.882 AC: 29621 AN: 33578

South Asian (SAS) AF: 0.964 AC: 53869 AN: 55896

European-Finnish (FIN) AF: 0.987 AC: 33393 AN: 33824

Middle Eastern (MID) AF: 0.953 AC: 2915 AN: 3058

European-Non Finnish (NFE) AF: 0.973 AC: 661300 AN: 679330

Other (OTH) AF: 0.940 AC: 38602 AN: 41058

GnomAD4 genome AF: 0.847 AC: 128895 AN: 152242 Hom.: 57351 Cov.: 33 AF XY: 0.851 AC XY: 63374 AN XY: 74442

African (AFR) AF: 0.541 AC: 22447 AN: 41486

American (AMR) AF: 0.931 AC: 14244 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 3409 AN: 3472

East Asian (EAS) AF: 0.882 AC: 4570 AN: 5180

South Asian (SAS) AF: 0.958 AC: 4625 AN: 4828

European-Finnish (FIN) AF: 0.989 AC: 10505 AN: 10620

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.971 AC: 66053 AN: 68036

Other (OTH) AF: 0.887 AC: 1873 AN: 2112

Alfa AF: 0.902 Hom.: 7932

Bravo AF: 0.829

Asia WGS AF: 0.893 AC: 3106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.084
DANN	Benign	0.38
PhyloP100		-2.0
Mutation Taster		=11/89	disease causing

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: rs1397618; hg19: chr10-120832675;