chr11-65998651-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001242481.2(EIF1AD):​c.446G>A​(p.Arg149His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000427 in 1,614,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: EIF1AD NM_001242481.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09279883).

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>A	p.Arg149His	missense	Exon 6 of 6	NP_001229410.1	Q8N9N8
	EIF1AD	NM_001242482.2		c.446G>A	p.Arg149His	missense	Exon 6 of 6	NP_001229411.1	Q8N9N8
	EIF1AD	NM_001242483.2		c.446G>A	p.Arg149His	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>A	p.Arg149His	missense	Exon 6 of 6	ENSP00000434056.1	Q8N9N8
	EIF1AD	ENST00000312234.6	TSL:1	c.446G>A	p.Arg149His	missense	Exon 6 of 6	ENSP00000309175.2	Q8N9N8
	EIF1AD	ENST00000526451.5	TSL:1	c.446G>A	p.Arg149His	missense	Exon 6 of 6	ENSP00000436644.1	Q8N9N8

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 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: 0.000577

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000557 AC: 14 AN: 251462 AF XY: 0.0000515

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000438 AC: 64 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32 AN XY: 727232

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

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

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

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5762

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1112000

Other (OTH) AF: 0.0000497 AC: 3 AN: 60394

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74436

African (AFR) AF: 0.0000241 AC: 1 AN: 41526

American (AMR) AF: 0.00 AC: 0 AN: 15292

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

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.046
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.3
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.035
Sift	Benign	0.076	T
Sift4G	Benign	0.084	T
Polyphen		0.20	B
Vest4		0.14
MVP		0.42
MPC		0.15
ClinPred		0.18	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.12
gMVP		0.33
Mutation Taster		=43/57	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; COSMIC: COSV56463852; COSMIC: COSV56463852;