chr14-103339164-C-T

Variant names:

• chr14-103339164-C-T
• rs115589341
• NM_001969.5:c.745-8C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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 Likely 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/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.12
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -20 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/Likely_benign. ClinVar VariationId is 714525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001969.5. 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
	EIF5	NM_001969.5	MANE Select	c.745-8C>T		splice_region intron	N/A	NP_001960.2
	EIF5	NM_183004.5		c.745-8C>T		splice_region intron	N/A	NP_892116.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF5	ENST00000216554.8	TSL:1 MANE Select	c.745-8C>T		splice_region intron	N/A	ENSP00000216554.3	P55010
	EIF5	ENST00000392715.6	TSL:1	c.745-8C>T		splice_region intron	N/A	ENSP00000376477.2	P55010
	EIF5	ENST00000558506.1	TSL:1	c.745-8C>T		splice_region intron	N/A	ENSP00000453743.1	P55010

Frequencies

GnomAD3 genomes AF: 0.00699 AC: 1063 AN: 152148 Hom.: 11 Cov.: 33

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

GnomAD2 exomes AF: 0.00209 AC: 496 AN: 236764 AF XY: 0.00145

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 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.: 13 Cov.: 31 AF XY: 0.000792 AC XY: 570 AN XY: 720118

African (AFR) AF: 0.0269 AC: 868 AN: 32256

American (AMR) AF: 0.00109 AC: 44 AN: 40454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25378

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39632

South Asian (SAS) AF: 0.000108 AC: 9 AN: 83330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53206

Middle Eastern (MID) AF: 0.00281 AC: 16 AN: 5688

European-Non Finnish (NFE) AF: 0.000204 AC: 226 AN: 1108114

Other (OTH) AF: 0.00218 AC: 130 AN: 59736

GnomAD4 genome AF: 0.00699 AC: 1064 AN: 152266 Hom.: 11 Cov.: 33 AF XY: 0.00655 AC XY: 488 AN XY: 74448

African (AFR) AF: 0.0242 AC: 1007 AN: 41548

American (AMR) AF: 0.00235 AC: 36 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68024

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00288 Hom.: 5

Bravo AF: 0.00816

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.58
DANN	Benign	0.76
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs115589341; hg19: chr14-103805501;