Genetic Variant NM_001143832.2:c.-84+2158G>A (chr19-39778833-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001143832.2(LEUTX):c.-84+2158G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,980 control chromosomes in the GnomAD database, including 5,835 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 0.26 ( 5833 hom., cov: 31)

Exomes 𝑓: 0.30 ( 2 hom. )

Consequence

LEUTX
NM_001143832.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.188

Publications

4 publications found

Variant links:

Genes affected

LEUTX (HGNC:31953): (leucine twenty homeobox) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LEUTX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LEUTX	NM_001143832.2 link	c.-84+2158G>A		intron_variant	Intron 1 of 2		NP_001137304.1	A8MZ59-1
LEUTX	NM_001382345.1 link	c.-88G>A		upstream_gene_variant		ENST00000638280.2	NP_001369274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LEUTX	ENST00000396841.4 link	c.-84+2158G>A		intron_variant	Intron 1 of 2	2		ENSP00000380053.3		A8MZ59-1
LEUTX	ENST00000638280.2 link	c.-88G>A		upstream_gene_variant		3	NM_001382345.1	ENSP00000491740.1		A8MZ59-2

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39692

AN:

151798

Hom.:

5833

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.273

GnomAD4 exome

AF:

0.297

AC:

AN:

Hom.:

Cov.:

AF XY:

0.364

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.111

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.381

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.261

AC:

39697

AN:

151916

Hom.:

5833

Cov.:

AF XY:

0.264

AC XY:

19565

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.121

AC:

5024

AN:

41468

American (AMR)

AF:

0.300

AC:

4577

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1190

AN:

3472

East Asian (EAS)

AF:

0.489

AC:

2521

AN:

5154

South Asian (SAS)

AF:

0.376

AC:

1807

AN:

4806

European-Finnish (FIN)

AF:

0.271

AC:

2853

AN:

10520

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.303

AC:

20612

AN:

67932

Other (OTH)

AF:

0.278

AC:

587

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1414

2828

4241

5655

7069

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.294

Hom.:

29198

Bravo

AF:

0.261

Asia WGS

AF:

0.399

AC:

1384

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.6

(source)

DANN

Benign

0.52

PhyloP100

0.19

PromoterAI

0.027

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over