Genetic Variant ENST00000361198.9:c.-593G>A (chr10-102114915-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000361198.9(LDB1):c.-593G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 876,016 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

LDB1
ENST00000361198.9 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.989

Publications

1 publications found

Variant links:

Genes affected

LDB1 (HGNC:6532): (LIM domain binding 1) Enables LIM domain binding activity; RNA polymerase II-specific DNA-binding transcription factor binding activity; and enzyme binding activity. Involved in negative regulation of transcription, DNA-templated and positive regulation of transcription by RNA polymerase II. Located in chromatin. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

LDB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361198.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LDB1	NM_001113407.3	MANE Select	c.26-3379G>A	intron	N/A	NP_001106878.1	Q86U70-1
LDB1	NM_003893.5		c.-593G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_003884.1	Q86U70-2
LDB1	NM_003893.5		c.-593G>A	5_prime_UTR	Exon 1 of 11	NP_003884.1	Q86U70-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LDB1	ENST00000361198.9	TSL:1	c.-593G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000354616.5	Q86U70-2
LDB1	ENST00000361198.9	TSL:1	c.-593G>A	5_prime_UTR	Exon 1 of 11	ENSP00000354616.5	Q86U70-2
LDB1	ENST00000673968.1	MANE Select	c.26-3379G>A	intron	N/A	ENSP00000501277.1	Q86U70-1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000828

AC:

AN:

724384

Hom.:

Cov.:

AF XY:

0.00000594

AC XY:

AN XY:

336732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13712

American (AMR)

AF:

0.00

AC:

AN:

888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4452

East Asian (EAS)

AF:

0.00

AC:

AN:

3094

South Asian (SAS)

AF:

0.00

AC:

AN:

14354

European-Finnish (FIN)

AF:

0.00

AC:

AN:

232

Middle Eastern (MID)

AF:

0.000696

AC:

AN:

1436

European-Non Finnish (NFE)

AF:

0.00000755

AC:

AN:

662434

Other (OTH)

AF:

0.00

AC:

AN:

23782

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151632

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74102

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41390

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000197

AC:

AN:

5070

South Asian (SAS)

AF:

0.00

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67840

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.99

PromoterAI

-0.15

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over