chr22-31460135-A-G

Variant names:

• chr22-31460135-A-G
• rs10483159
• NM_019843.4:c.788-1485T>C

Variant summary

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

The NM_019843.4(EIF4ENIF1):​c.788-1485T>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
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019843.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4ENIF1	NM_019843.4	MANE Select	c.788-1485T>C		intron	N/A	NP_062817.2
	EIF4ENIF1	NM_001164501.2		c.788-1485T>C		intron	N/A	NP_001157973.1
	EIF4ENIF1	NM_001164502.2		c.299-1485T>C		intron	N/A	NP_001157974.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4ENIF1	ENST00000330125.10	TSL:1 MANE Select	c.788-1485T>C		intron	N/A	ENSP00000328103.5
	EIF4ENIF1	ENST00000397525.5	TSL:1	c.788-1485T>C		intron	N/A	ENSP00000380659.1
	EIF4ENIF1	ENST00000344710.9	TSL:1	c.299-1485T>C		intron	N/A	ENSP00000342927.5

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

African (AFR) AF: 0.0950 AC: 3947 AN: 41560

American (AMR) AF: 0.0850 AC: 1299 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3468

East Asian (EAS) AF: 0.0694 AC: 360 AN: 5188

South Asian (SAS) AF: 0.0307 AC: 148 AN: 4826

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10618

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.00210 AC: 143 AN: 68040

Other (OTH) AF: 0.0279 AC: 59 AN: 2114

Alfa AF: 0.0144 Hom.: 21

Bravo AF: 0.0484

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		0.0030
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: rs10483159; hg19: chr22-31856121;