chr5-176635249-T-C

Variant names:

• chr5-176635249-T-C
• rs4868670
• NM_001099408.2:c.-202+4185T>C

Variant summary

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

The NM_001099408.2(EIF4E1B):​c.-202+4185T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 151,434 control chromosomes in the GnomAD database, including 12,963 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 0.39 (12963 hom., cov: 29)
• Consequence: EIF4E1B NM_001099408.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 2 publications found

Genes affected

EIF4E1B (HGNC:33179): (eukaryotic translation initiation factor 4E family member 1B) Predicted to enable RNA 7-methylguanosine cap binding activity and translation initiation factor activity. Predicted to be involved in regulation of translation and translational initiation. Predicted to be located in cytoplasm. Predicted to be part of eukaryotic translation initiation factor 4F complex and mRNA cap binding activity complex. [provided by Alliance of Genome Resources, Apr 2022]

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 (NFE) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099408.2. 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
	EIF4E1B	NM_001099408.2	MANE Select	c.-202+4185T>C		intron	N/A	NP_001092878.1	A6NMX2
	EIF4E1B	NM_001375362.1		c.-214+4185T>C		intron	N/A	NP_001362291.1	A6NMX2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF4E1B	ENST00000318682.11	TSL:5 MANE Select	c.-202+4185T>C		intron	N/A	ENSP00000323714.6	A6NMX2
	EIF4E1B	ENST00000647833.1		c.-359-2077T>C		intron	N/A	ENSP00000497422.1	A6NMX2
	EIF4E1B	ENST00000862451.1		c.-214+4185T>C		intron	N/A	ENSP00000532510.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 58998 AN: 151316 Hom.: 12953 Cov.: 29

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.0165

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.390 AC: 59022 AN: 151434 Hom.: 12963 Cov.: 29 AF XY: 0.383 AC XY: 28334 AN XY: 73998

African (AFR) AF: 0.237 AC: 9758 AN: 41228

American (AMR) AF: 0.448 AC: 6815 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1422 AN: 3464

East Asian (EAS) AF: 0.0163 AC: 84 AN: 5144

South Asian (SAS) AF: 0.244 AC: 1169 AN: 4786

European-Finnish (FIN) AF: 0.487 AC: 5099 AN: 10478

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.491 AC: 33278 AN: 67836

Other (OTH) AF: 0.389 AC: 816 AN: 2098

Alfa AF: 0.412 Hom.: 5461

Bravo AF: 0.381

Asia WGS AF: 0.140 AC: 491 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	1.9
DANN	Benign	0.46
PhyloP100		-0.35
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: rs4868670; hg19: chr5-176062250;