Variant X-20135846-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001412.4(EIF1AX):c.101-5G>A variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003420

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.595

Variant links:

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]

EIF1AX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 787515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-20135846-C-T is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF1AX	NM_001412.4 linkuse as main transcript	c.101-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000379607.10	NP_001403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF1AX	ENST00000379607.10 linkuse as main transcript	c.101-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001412.4	ENSP00000368927	P1
EIF1AX	ENST00000379593.1 linkuse as main transcript	c.17-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000368912

Frequencies

GnomAD3 genomes

AF:

0.00932

AC:

1042

AN:

111765

Hom.:

Cov.:

AF XY:

0.00854

AC XY:

290

AN XY:

33977

show subpopulations

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

GnomAD3 exomes

AF:

0.00296

AC:

541

AN:

182699

Hom.:

AF XY:

0.00211

AC XY:

142

AN XY:

67189

show subpopulations

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 SAS exome

AF:

0.0000529

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.:

Cov.:

AF XY:

0.00111

AC XY:

367

AN XY:

329590

show subpopulations

Gnomad4 AFR exome

AF:

0.0376

Gnomad4 AMR exome

AF:

0.00228

Gnomad4 ASJ exome

AF:

0.000105

Gnomad4 EAS exome

AF:

0.0000333

Gnomad4 SAS exome

AF:

0.0000753

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.00312

GnomAD4 genome

AF:

0.00934

AC:

1044

AN:

111820

Hom.:

Cov.:

AF XY:

0.00849

AC XY:

289

AN XY:

34040

show subpopulations

Gnomad4 AFR

AF:

0.0317

Gnomad4 AMR

AF:

0.00398

Gnomad4 ASJ

AF:

0.000377

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000940

Gnomad4 OTH

AF:

0.0117

Alfa

AF:

0.00591

Hom.:

Bravo

AF:

0.0105

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.22

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over