chr22-31458860-T-C

Variant names:

• chr22-31458860-T-C
• rs5753625
• NM_019843.4:c.788-210A>G

Variant summary

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

The NM_019843.4(EIF4ENIF1):​c.788-210A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 150,930 control chromosomes in the GnomAD database, including 11,162 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 0.36 (11162 hom., cov: 29)
• Consequence: EIF4ENIF1 NM_019843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 10 publications found

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]

ENSG00000240591 (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]

DRG1 Gene-Disease associations (from GenCC):

• Tan-Almurshedi syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4ENIF1	NM_019843.4	c.788-210A>G		intron_variant	Intron 6 of 18	ENST00000330125.10	NP_062817.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4ENIF1	ENST00000330125.10	c.788-210A>G		intron_variant	Intron 6 of 18	1	NM_019843.4	ENSP00000328103.5

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54227 AN: 150832 Hom.: 11152 Cov.: 29

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.360 AC: 54273 AN: 150930 Hom.: 11162 Cov.: 29 AF XY: 0.366 AC XY: 26946 AN XY: 73566

African (AFR) AF: 0.215 AC: 8826 AN: 41114

American (AMR) AF: 0.418 AC: 6317 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3464

East Asian (EAS) AF: 0.870 AC: 4454 AN: 5122

South Asian (SAS) AF: 0.487 AC: 2331 AN: 4790

European-Finnish (FIN) AF: 0.412 AC: 4200 AN: 10184

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.385 AC: 26125 AN: 67870

Other (OTH) AF: 0.336 AC: 702 AN: 2088

Alfa AF: 0.381 Hom.: 5336

Bravo AF: 0.354

Asia WGS AF: 0.641 AC: 2226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		-0.31
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: rs5753625; hg19: chr22-31854846;