chr22-31440392-G-T

Variant names:

• chr22-31440392-G-T
• rs4820972
• NM_019843.4:c.2717-271C>A

Variant summary

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

The NM_019843.4(EIF4ENIF1):​c.2717-271C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 152,156 control chromosomes in the GnomAD database, including 65,303 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 0.93 (65303 hom., cov: 30)
• Consequence: EIF4ENIF1 NM_019843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4ENIF1	NM_019843.4	MANE Select	c.2717-271C>A		intron	N/A	NP_062817.2	Q9NRA8-1
	EIF4ENIF1	NM_001164501.2		c.2717-271C>A		intron	N/A	NP_001157973.1	Q9NRA8-1
	EIF4ENIF1	NM_001164502.2		c.2195-271C>A		intron	N/A	NP_001157974.1	Q9NRA8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4ENIF1	ENST00000330125.10	TSL:1 MANE Select	c.2717-271C>A		intron	N/A	ENSP00000328103.5	Q9NRA8-1
	EIF4ENIF1	ENST00000397525.5	TSL:1	c.2717-271C>A		intron	N/A	ENSP00000380659.1	Q9NRA8-1
	EIF4ENIF1	ENST00000344710.9	TSL:1	c.2195-271C>A		intron	N/A	ENSP00000342927.5	Q9NRA8-2

Frequencies

GnomAD3 genomes AF: 0.926 AC: 140784 AN: 152038 Hom.: 65258 Cov.: 30

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.958

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.911

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

GnomAD4 genome AF: 0.926 AC: 140885 AN: 152156 Hom.: 65303 Cov.: 30 AF XY: 0.927 AC XY: 68957 AN XY: 74392

African (AFR) AF: 0.925 AC: 38396 AN: 41514

American (AMR) AF: 0.847 AC: 12938 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 3194 AN: 3470

East Asian (EAS) AF: 0.991 AC: 5113 AN: 5162

South Asian (SAS) AF: 0.972 AC: 4676 AN: 4812

European-Finnish (FIN) AF: 0.958 AC: 10156 AN: 10606

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.932 AC: 63346 AN: 67996

Other (OTH) AF: 0.912 AC: 1928 AN: 2114

Alfa AF: 0.927 Hom.: 129735

Bravo AF: 0.917

Asia WGS AF: 0.957 AC: 3328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.069
DANN	Benign	0.44
PhyloP100		-1.0
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: rs4820972; hg19: chr22-31836378;