chr14-103339164-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001969.5(EIF5):​c.745-8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EIF5 NM_001969.5 splice_region, intron
• Scores: Splicing: ADA: 0.00006642
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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>G		splice_region intron	N/A	NP_001960.2
	EIF5	NM_183004.5		c.745-8C>G		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>G		splice_region intron	N/A	ENSP00000216554.3	P55010
	EIF5	ENST00000392715.6	TSL:1	c.745-8C>G		splice_region intron	N/A	ENSP00000376477.2	P55010
	EIF5	ENST00000558506.1	TSL:1	c.745-8C>G		splice_region intron	N/A	ENSP00000453743.1	P55010

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1447802 Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2 AN XY: 720120

African (AFR) AF: 0.00 AC: 0 AN: 32258

American (AMR) AF: 0.00 AC: 0 AN: 40456

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.0000240 AC: 2 AN: 83330

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108118

Other (OTH) AF: 0.00 AC: 0 AN: 59736

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.51
DANN	Benign	0.74
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000066
dbscSNV1_RF	Benign	0.014
SpliceAI score (max)		0.010		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;