dbSNP rs3758554: LDB1: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDB1	NM_001113407.3 link	c.26-3379G>C		intron_variant	Intron 1 of 10	ENST00000673968.1	NP_001106878.1	Q86U70-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LDB1	ENST00000361198.9 link	c.-593G>C	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 11	1		ENSP00000354616.5	Q86U70-2
LDB1	ENST00000361198.9 link	c.-593G>C	5_prime_UTR_variant	Exon 1 of 11	1		ENSP00000354616.5	Q86U70-2
LDB1	ENST00000673968.1 link	c.26-3379G>C	intron_variant	Intron 1 of 10		NM_001113407.3	ENSP00000501277.1	Q86U70-1
LDB1	ENST00000425280.2 link	c.26-3379G>C	intron_variant	Intron 1 of 10	5		ENSP00000392466.2	A0A6E1WJ75

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 v4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over