rs3758554

chr10-102114915-C-Gchr10-102114915-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000361198.9(LDB1):c.-593G>C variant causes a 5 prime UTR 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.989

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 -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/exons	MANE	UniProt
LDB1	NM_001113407.3	c.26-3379G>C		intron_variant		ENST00000673968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LDB1	ENST00000361198.9	c.-593G>C		5_prime_UTR_variant	1/11	1		A1
LDB1	ENST00000673968.1	c.26-3379G>C		intron_variant			NM_001113407.3	P4
LDB1	ENST00000425280.2	c.26-3379G>C		intron_variant		5		A1

Frequencies

GnomAD3 genomes AF: 0.00405 AC: 614 AN: 151516 Hom.: 9 Cov.: 31

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.: 8 Cov.: 10 AF XY: 0.00189 AC XY: 637 AN XY: 336714

Gnomad4 AFR exome AF: 0.000511

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00292

Gnomad4 EAS exome AF: 0.0631

Gnomad4 SAS exome AF: 0.00320

Gnomad4 FIN exome AF: 0.00862

Gnomad4 NFE exome AF: 0.00163

Gnomad4 OTH exome AF: 0.00458

GnomAD4 genome AF: 0.00406 AC: 615 AN: 151630 Hom.: 9 Cov.: 31 AF XY: 0.00490 AC XY: 363 AN XY: 74100

Gnomad4 AFR AF: 0.000411

Gnomad4 AMR AF: 0.000721

Gnomad4 ASJ AF: 0.00462

Gnomad4 EAS AF: 0.0625

Gnomad4 SAS AF: 0.00376

Gnomad4 FIN AF: 0.00960

Gnomad4 NFE AF: 0.00187

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.00335

Asia WGS AF: 0.0210 AC: 73 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	19
Dann	Benign	0.90

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

LitVar

Other links and lift over

dbSNP: rs3758554; hg19: chr10-103874672;