Genetic Variant ENST00000361198.9:c.-593G>C (chr10-102114915-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000361198.9(LDB1):c.-593G>C 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 0.00236 in 875,980 control chromosomes in the GnomAD database, including 17 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 0.0041 ( 9 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 8 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

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>C	intron	N/A	NP_001106878.1	Q86U70-1
LDB1	NM_003893.5		c.-593G>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_003884.1	Q86U70-2
LDB1	NM_003893.5		c.-593G>C	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>C	5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000354616.5	Q86U70-2
LDB1	ENST00000361198.9	TSL:1	c.-593G>C	5_prime_UTR	Exon 1 of 11	ENSP00000354616.5	Q86U70-2
LDB1	ENST00000673968.1	MANE Select	c.26-3379G>C	intron	N/A	ENSP00000501277.1	Q86U70-1

Frequencies

GnomAD3 genomes

AF:

0.00405

AC:

614

AN:

151516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000412

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000722

Gnomad ASJ

AF:

0.00462

Gnomad EAS

AF:

0.0622

Gnomad SAS

AF:

0.00375

Gnomad FIN

AF:

0.00960

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00187

Gnomad OTH

AF:

0.00384

GnomAD4 exome

AF:

0.00200

AC:

1451

AN:

724350

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

637

AN XY:

336714

show subpopulations

African (AFR)

AF:

0.000511

AC:

AN:

13712

American (AMR)

AF:

0.00

AC:

AN:

888

Ashkenazi Jewish (ASJ)

AF:

0.00292

AC:

AN:

4450

East Asian (EAS)

AF:

0.0631

AC:

195

AN:

3092

South Asian (SAS)

AF:

0.00320

AC:

AN:

14354

European-Finnish (FIN)

AF:

0.00862

AC:

AN:

232

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

1434

European-Non Finnish (NFE)

AF:

0.00163

AC:

1077

AN:

662412

Other (OTH)

AF:

0.00458

AC:

109

AN:

23776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

130

196

261

326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.00406

AC:

615

AN:

151630

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

363

AN XY:

74100

show subpopulations

African (AFR)

AF:

0.000411

AC:

AN:

41390

American (AMR)

AF:

0.000721

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00462

AC:

AN:

3464

East Asian (EAS)

AF:

0.0625

AC:

317

AN:

5068

South Asian (SAS)

AF:

0.00376

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00960

AC:

101

AN:

10516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00187

AC:

127

AN:

67840

Other (OTH)

AF:

0.00380

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

130

162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00111

Hom.:

Bravo

AF:

0.00335

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

0.99

PromoterAI

0.056

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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