rs10483159

Positions:

• chr22-31460135-A-G
• chr22-31460135-A-T

Variant summary

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

The NM_019843.4(EIF4ENIF1):​c.788-1485T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 152,308 control chromosomes in the GnomAD database, including 283 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 0.039 (283 hom., cov: 32)
• Consequence: EIF4ENIF1 NM_019843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300

Genes affected

EIF4ENIF1 (HGNC:16687): (eukaryotic translation initiation factor 4E nuclear import factor 1) The protein encoded by this gene is a nucleocytoplasmic shuttle protein for the translation initiation factor eIF4E. This shuttle protein interacts with the importin alpha-beta complex to mediate nuclear import of eIF4E. It is predominantly cytoplasmic; its own nuclear import is regulated by a nuclear localization signal and nuclear export signals. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

(HGNC:):

DRG1 (HGNC:3029): (developmentally regulated GTP binding protein 1) Enables several functions, including GTPase activity; identical protein binding activity; and potassium ion binding activity. Involved in positive regulation of microtubule polymerization and regulation of mitotic spindle assembly. Located in cytosol and nuclear body. Part of polysome. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4ENIF1	NM_019843.4	c.788-1485T>C		intron_variant		ENST00000330125.10	NP_062817.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4ENIF1	ENST00000330125.10	c.788-1485T>C		intron_variant		1	NM_019843.4	ENSP00000328103	P1
	ENST00000655902.1	n.1544-3595A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5979 AN: 152190 Hom.: 279 Cov.: 32

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.0690

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.0282

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

GnomAD4 genome AF: 0.0394 AC: 6006 AN: 152308 Hom.: 283 Cov.: 32 AF XY: 0.0412 AC XY: 3069 AN XY: 74482

Gnomad4 AFR AF: 0.0950

Gnomad4 AMR AF: 0.0850

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.0694

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00210

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0129 Hom.: 19

Bravo AF: 0.0484

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.68

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: rs10483159; hg19: chr22-31856121;