chr11-65998651-C-A

Variant names:

• chr11-65998651-C-A
• rs767908582
• NM_001242481.2:c.446G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001242481.2(EIF1AD):​c.446G>T​(p.Arg149Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R149C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EIF1AD NM_001242481.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.26
• Publications: 0 publications found

Genes affected

EIF1AD (HGNC:28147): (eukaryotic translation initiation factor 1A domain containing) Predicted to enable translation initiation factor activity. Predicted to be involved in translational initiation. Located in intermediate filament cytoskeleton and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242481.2. 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
	EIF1AD	NM_001242481.2	MANE Select	c.446G>T	p.Arg149Leu	missense	Exon 6 of 6	NP_001229410.1	Q8N9N8
	EIF1AD	NM_001242482.2		c.446G>T	p.Arg149Leu	missense	Exon 6 of 6	NP_001229411.1	Q8N9N8
	EIF1AD	NM_001242483.2		c.446G>T	p.Arg149Leu	missense	Exon 6 of 6	NP_001229412.1	Q8N9N8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF1AD	ENST00000533544.6	TSL:3 MANE Select	c.446G>T	p.Arg149Leu	missense	Exon 6 of 6	ENSP00000434056.1	Q8N9N8
	EIF1AD	ENST00000312234.6	TSL:1	c.446G>T	p.Arg149Leu	missense	Exon 6 of 6	ENSP00000309175.2	Q8N9N8
	EIF1AD	ENST00000526451.5	TSL:1	c.446G>T	p.Arg149Leu	missense	Exon 6 of 6	ENSP00000436644.1	Q8N9N8

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727232

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74308

African (AFR) AF: 0.0000242 AC: 1 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.3
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.46
MutPred		0.45		Loss of phosphorylation at T147 (P = 0.0676)
MVP		0.68
MPC		0.48
ClinPred		1.0	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.50
gMVP		0.45
Mutation Taster		=36/64	disease causing

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: rs767908582; hg19: chr11-65766122;