Genetic Variant EIF5:c.745-8C>T (chr14-103339164-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001969.5(EIF5):c.745-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,600,060 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 11 hom., cov: 33)

Exomes 𝑓: 0.00089 ( 13 hom. )

Consequence

EIF5
NM_001969.5 splice_region, intron

Scores

Splicing: ADA: 0.00003040

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.12

Variant links:

Genes affected

EIF5 (HGNC:3299): (eukaryotic translation initiation factor 5) Eukaryotic translation initiation factor-5 (EIF5) interacts with the 40S initiation complex to promote hydrolysis of bound GTP with concomitant joining of the 60S ribosomal subunit to the 40S initiation complex. The resulting functional 80S ribosomal initiation complex is then active in peptidyl transfer and chain elongations (summary by Si et al., 1996 [PubMed 8663286]).[supplied by OMIM, May 2010]

EIF5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-103339164-C-T is Benign according to our data. Variant chr14-103339164-C-T is described in ClinVar as [Benign]. Clinvar id is 714525.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00699 (1064/152266) while in subpopulation AFR AF= 0.0242 (1007/41548). AF 95% confidence interval is 0.023. There are 11 homozygotes in gnomad4. There are 488 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF5	NM_001969.5 link	c.745-8C>T		splice_region_variant, intron_variant	Intron 8 of 11	ENST00000216554.8	NP_001960.2	P55010A0A024R6Q1
EIF5	NM_183004.5 link	c.745-8C>T		splice_region_variant, intron_variant	Intron 7 of 10		NP_892116.2	P55010A0A024R6Q1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EIF5	ENST00000216554.8 link	c.745-8C>T	splice_region_variant, intron_variant	Intron 8 of 11	1	NM_001969.5	ENSP00000216554.3	P55010
EIF5	ENST00000392715.6 link	c.745-8C>T	splice_region_variant, intron_variant	Intron 7 of 10	1		ENSP00000376477.2	P55010
EIF5	ENST00000558506.1 link	c.745-8C>T	splice_region_variant, intron_variant	Intron 6 of 9	1		ENSP00000453743.1	P55010
EIF5	ENST00000561380.1 link	n.160-8C>T	splice_region_variant, intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.00699

AC:

1063

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00209

AC:

496

AN:

236764

Hom.:

AF XY:

0.00145

AC XY:

186

AN XY:

128194

show subpopulations

Gnomad AFR exome

AF:

0.0279

Gnomad AMR exome

AF:

0.000881

Gnomad ASJ exome

AF:

0.000109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000732

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000174

Gnomad OTH exome

AF:

0.000528

GnomAD4 exome

AF:

0.000894

AC:

1294

AN:

1447794

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

570

AN XY:

720118

show subpopulations

Gnomad4 AFR exome

AF:

0.0269

Gnomad4 AMR exome

AF:

0.00109

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000108

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.00218

GnomAD4 genome

AF:

0.00699

AC:

1064

AN:

152266

Hom.:

Cov.:

AF XY:

0.00655

AC XY:

488

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0242

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.00816

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.58

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000030

dbscSNV1_RF

Benign

0.0020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over