5-126776888-T-C

Position:

• chr5-126776888-T-C

Variant summary

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

The ENST00000460265.5(LMNB1):​c.-621T>C variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,036 control chromosomes in the GnomAD database, including 3,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3301 hom., cov: 33)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: LMNB1 ENST00000460265.5 5_prime_UTR, NMD_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.432

Genes affected

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 5-126776888-T-C is Benign according to our data. Variant chr5-126776888-T-C is described in ClinVar as [Benign]. Clinvar id is 350599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMNB1	NR_134488.1	n.266T>C		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMNB1	ENST00000460265.5	c.-621T>C		5_prime_UTR_variant, NMD_transcript_variant	1/12	1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30996 AN: 151846 Hom.: 3299 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0498

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.135 AC: 10 AN: 74 Hom.: 0 Cov.: 0 AF XY: 0.100 AC XY: 5 AN XY: 50

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.204 AC: 31017 AN: 151962 Hom.: 3301 Cov.: 33 AF XY: 0.207 AC XY: 15362 AN XY: 74296

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.203

Alfa AF: 0.206 Hom.: 396

Bravo AF: 0.205

Asia WGS AF: 0.230 AC: 799 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leukodystrophy, Adult-Onset Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
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: rs35091677; hg19: chr5-126112580;