22-31488419-T-C

Variant names:

• chr22-31488419-T-C
• rs7289941
• NM_019843.4:c.96+204A>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.96+204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,998 control chromosomes in the GnomAD database, including 16,407 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 0.46 (16407 hom., cov: 31)
• Consequence: EIF4ENIF1 NM_019843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381
• Publications: 6 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]

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF4ENIF1	NM_019843.4	c.96+204A>G		intron_variant	Intron 2 of 18	ENST00000330125.10	NP_062817.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF4ENIF1	ENST00000330125.10	c.96+204A>G		intron_variant	Intron 2 of 18	1	NM_019843.4	ENSP00000328103.5

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69774 AN: 151880 Hom.: 16400 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.459 AC: 69819 AN: 151998 Hom.: 16407 Cov.: 31 AF XY: 0.455 AC XY: 33801 AN XY: 74284

African (AFR) AF: 0.507 AC: 21027 AN: 41438

American (AMR) AF: 0.436 AC: 6657 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2057 AN: 3472

East Asian (EAS) AF: 0.159 AC: 819 AN: 5162

South Asian (SAS) AF: 0.402 AC: 1934 AN: 4814

European-Finnish (FIN) AF: 0.418 AC: 4405 AN: 10544

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31254 AN: 67978

Other (OTH) AF: 0.488 AC: 1033 AN: 2116

Alfa AF: 0.451 Hom.: 13190

Bravo AF: 0.464

Asia WGS AF: 0.281 AC: 976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.8
DANN	Benign	0.53
PhyloP100		0.38
PromoterAI		0.015	Neutral
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: rs7289941; hg19: chr22-31884405;