5-126776477-T-C

Variant names:

• chr5-126776477-T-C
• rs116519295
• ENST00000509185.2:n.10A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NR_134485.1(LMNB1-DT):​n.10A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 152,260 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (104 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: LMNB1-DT NR_134485.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.11

Genes affected

LMNB1-DT (HGNC:53089): (LMNB1 divergent transcript)

LMNB1 (HGNC:6637): (lamin B1) This gene encodes one of the two B-type lamin proteins and is a component of the nuclear lamina. A duplication of this gene is associated with autosomal dominant adult-onset leukodystrophy (ADLD). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-126776477-T-C is Benign according to our data. Variant chr5-126776477-T-C is described in ClinVar as [Benign]. Clinvar id is 1235155.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMNB1-DT	NR_134485.1	n.10A>G		non_coding_transcript_exon_variant	Exon 1 of 4
LMNB1	NR_134488.1	n.-146T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMNB1-DT	ENST00000509185.2	n.10A>G		non_coding_transcript_exon_variant	Exon 1 of 4	5
LMNB1	ENST00000460265.5	n.-1032T>C		upstream_gene_variant		1		ENSP00000486528.1

Frequencies

GnomAD3 genomes AF: 0.0314 AC: 4770 AN: 152138 Hom.: 104 Cov.: 33

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0406

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0313 AC: 4766 AN: 152256 Hom.: 104 Cov.: 33 AF XY: 0.0307 AC XY: 2282 AN XY: 74450

Gnomad4 AFR AF: 0.0537

Gnomad4 AMR AF: 0.0352

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.0332

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0322 Hom.: 8

Bravo AF: 0.0325

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.79
DANN	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs116519295; hg19: chr5-126112169;