dbSNP rs1046399: LDB1:c.*459C>T (chr10-102107634-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_001113407.3(LDB1):c.*459C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 156,832 control chromosomes in the GnomAD database, including 1,745 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 0.095 ( 1742 hom., cov: 31)

Exomes 𝑓: 0.020 ( 3 hom. )

Consequence

LDB1
NM_001113407.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

Publications

2 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 -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113407.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LDB1	NM_001113407.3	MANE Select	c.*459C>T	3_prime_UTR	Exon 11 of 11	NP_001106878.1
LDB1	NM_001321612.2		c.*459C>T	3_prime_UTR	Exon 11 of 11	NP_001308541.1
LDB1	NM_003893.5		c.*459C>T	3_prime_UTR	Exon 11 of 11	NP_003884.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LDB1	ENST00000673968.1	MANE Select	c.*459C>T	3_prime_UTR	Exon 11 of 11	ENSP00000501277.1
LDB1	ENST00000361198.9	TSL:1	c.*459C>T	3_prime_UTR	Exon 11 of 11	ENSP00000354616.5
LDB1	ENST00000425280.2	TSL:5	c.*459C>T	3_prime_UTR	Exon 11 of 11	ENSP00000392466.2

Frequencies

GnomAD3 genomes

AF:

0.0950

AC:

14432

AN:

151904

Hom.:

1738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0415

Gnomad ASJ

AF:

0.0369

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0297

Gnomad FIN

AF:

0.00274

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0213

Gnomad OTH

AF:

0.0731

GnomAD4 exome

AF:

0.0195

AC:

AN:

4812

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

AN XY:

2496

show subpopulations

African (AFR)

AF:

0.245

AC:

AN:

American (AMR)

AF:

0.0242

AC:

AN:

496

Ashkenazi Jewish (ASJ)

AF:

0.0530

AC:

AN:

132

East Asian (EAS)

AF:

0.00568

AC:

AN:

176

South Asian (SAS)

AF:

0.0175

AC:

AN:

228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

366

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0131

AC:

AN:

3058

Other (OTH)

AF:

0.0278

AC:

AN:

252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.0951

AC:

14451

AN:

152020

Hom.:

1742

Cov.:

AF XY:

0.0908

AC XY:

6752

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.287

AC:

11887

AN:

41392

American (AMR)

AF:

0.0414

AC:

633

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0369

AC:

128

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5184

South Asian (SAS)

AF:

0.0293

AC:

141

AN:

4812

European-Finnish (FIN)

AF:

0.00274

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0582

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0213

AC:

1447

AN:

67972

Other (OTH)

AF:

0.0723

AC:

152

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

547

1094

1640

2187

2734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<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:

0.0510

Hom.:

218

Bravo

AF:

0.107

Asia WGS

AF:

0.0290

AC:

104

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.3

(source)

DANN

Benign

0.63

PhyloP100

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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