chrX-20135846-C-T

Variant names:

• chrX-20135846-C-T
• rs5955886
• NM_001412.4:c.101-5G>A

Variant summary

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

The NM_001412.4(EIF1AX):​c.101-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,172,190 control chromosomes in the GnomAD database, including 27 homozygotes. There are 656 hemizygotes in GnomAD. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (13 hom., 289 hem., cov: 23)
  • Exomes 𝑓: 0.0012 (14 hom. 367 hem.)
• Consequence: EIF1AX NM_001412.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003420
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.595
• Publications: 2 publications found

Genes affected

EIF1AX (HGNC:3250): (eukaryotic translation initiation factor 1A X-linked) This gene encodes an essential eukaryotic translation initiation factor. The protein is required for the binding of the 43S complex (a 40S subunit, eIF2/GTP/Met-tRNAi and eIF3) to the 5' end of capped RNA. [provided by RefSeq, Jul 2008]

ENSG00000201882 (HGNC:):

SCARNA9L (HGNC:33559): (small Cajal body-specific RNA 9 like)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant X-20135846-C-T is Benign according to our data. Variant chrX-20135846-C-T is described in ClinVar as Benign. ClinVar VariationId is 787515.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 = 0.00934 (1044/111820) while in subpopulation AFR AF = 0.0317 (976/30759). AF 95% confidence interval is 0.0301. There are 13 homozygotes in GnomAd4. There are 289 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001412.4. 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
	EIF1AX	NM_001412.4	MANE Select	c.101-5G>A		splice_region intron	N/A	NP_001403.1	P47813
	SCARNA9L	NR_023358.1		n.*220G>A		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF1AX	ENST00000379607.10	TSL:1 MANE Select	c.101-5G>A		splice_region intron	N/A	ENSP00000368927.5	P47813
	EIF1AX	ENST00000914219.1		c.95-5G>A		splice_region intron	N/A	ENSP00000584278.1
	EIF1AX	ENST00000914220.1		c.92-5G>A		splice_region intron	N/A	ENSP00000584279.1

Frequencies

GnomAD3 genomes AF: 0.00932 AC: 1042 AN: 111765 Hom.: 13 Cov.: 23

Gnomad AFR AF: 0.0317

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00398

Gnomad ASJ AF: 0.000377

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.0000940

Gnomad OTH AF: 0.0119

GnomAD2 exomes AF: 0.00296 AC: 541 AN: 182699 AF XY: 0.00211

Gnomad AFR exome AF: 0.0344

Gnomad AMR exome AF: 0.00195

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000257

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00125 AC: 1321 AN: 1060370 Hom.: 14 Cov.: 24 AF XY: 0.00111 AC XY: 367 AN XY: 329590

African (AFR) AF: 0.0376 AC: 967 AN: 25690

American (AMR) AF: 0.00228 AC: 80 AN: 35022

Ashkenazi Jewish (ASJ) AF: 0.000105 AC: 2 AN: 19103

East Asian (EAS) AF: 0.0000333 AC: 1 AN: 30011

South Asian (SAS) AF: 0.0000753 AC: 4 AN: 53133

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40464

Middle Eastern (MID) AF: 0.00621 AC: 25 AN: 4026

European-Non Finnish (NFE) AF: 0.000126 AC: 102 AN: 808096

Other (OTH) AF: 0.00312 AC: 140 AN: 44825

GnomAD4 genome AF: 0.00934 AC: 1044 AN: 111820 Hom.: 13 Cov.: 23 AF XY: 0.00849 AC XY: 289 AN XY: 34040

African (AFR) AF: 0.0317 AC: 976 AN: 30759

American (AMR) AF: 0.00398 AC: 42 AN: 10559

Ashkenazi Jewish (ASJ) AF: 0.000377 AC: 1 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3573

South Asian (SAS) AF: 0.00 AC: 0 AN: 2690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5978

Middle Eastern (MID) AF: 0.00913 AC: 2 AN: 219

European-Non Finnish (NFE) AF: 0.0000940 AC: 5 AN: 53174

Other (OTH) AF: 0.0117 AC: 18 AN: 1535

Alfa AF: 0.00591 Hom.: 32

Bravo AF: 0.0105

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.22
DANN	Benign	0.83
PhyloP100		-0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000034
dbscSNV1_RF	Benign	0.0080
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: rs5955886; hg19: chrX-20153964;