rs1046399

Positions:

• chr10-102107634-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LDB1	NM_001113407.3	c.*459C>T		3_prime_UTR_variant	11/11	ENST00000673968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDB1	ENST00000673968.1	c.*459C>T		3_prime_UTR_variant	11/11		NM_001113407.3	P4
LDB1	ENST00000361198.9	c.*459C>T		3_prime_UTR_variant	11/11	1		A1
LDB1	ENST00000425280.2	c.*459C>T		3_prime_UTR_variant	11/11	5		A1

Frequencies

GnomAD3 genomes AF: 0.0950 AC: 14432 AN: 151904 Hom.: 1738 Cov.: 31

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: 94 AN: 4812 Hom.: 3 Cov.: 0 AF XY: 0.0200 AC XY: 50 AN XY: 2496

Gnomad4 AFR exome AF: 0.245

Gnomad4 AMR exome AF: 0.0242

Gnomad4 ASJ exome AF: 0.0530

Gnomad4 EAS exome AF: 0.00568

Gnomad4 SAS exome AF: 0.0175

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0131

Gnomad4 OTH exome AF: 0.0278

GnomAD4 genome AF: 0.0951 AC: 14451 AN: 152020 Hom.: 1742 Cov.: 31 AF XY: 0.0908 AC XY: 6752 AN XY: 74328

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.0414

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0293

Gnomad4 FIN AF: 0.00274

Gnomad4 NFE AF: 0.0213

Gnomad4 OTH AF: 0.0723

Alfa AF: 0.0512 Hom.: 136

Bravo AF: 0.107

Asia WGS AF: 0.0290 AC: 104 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	5.3
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs1046399; hg19: chr10-103867391;