ENST00000509185.2:n.26G>T

Variant names:

• chr5-126776461-C-A
• rs2036844
• ENST00000509185.2:n.26G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000509185.2(LMNB1-DT):​n.26G>T 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 0.677 in 152,112 control chromosomes in the GnomAD database, including 35,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (35336 hom., cov: 33)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: LMNB1-DT ENST00000509185.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.51
• Publications: 4 publications found

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]

LMNB1 Gene-Disease associations (from GenCC):

• microcephaly 26, primary, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• adult-onset autosomal dominant demyelinating leukodystrophy

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• microcephaly

  Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox
• autosomal dominant primary microcephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 5-126776461-C-A is Benign according to our data. Variant chr5-126776461-C-A is described in ClinVar as Benign. ClinVar VariationId is 1179859.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000509185.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNB1-DT	NR_134485.1		n.26G>T		non_coding_transcript_exon	Exon 1 of 4
	LMNB1	NR_134488.1		n.-162C>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMNB1-DT	ENST00000509185.2	TSL:5	n.26G>T		non_coding_transcript_exon	Exon 1 of 4
	LMNB1-DT	ENST00000815038.1		n.86G>T		non_coding_transcript_exon	Exon 1 of 2
	LMNB1-DT	ENST00000815039.1		n.63G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102918 AN: 151990 Hom.: 35325 Cov.: 33

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.689

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.677 AC: 102978 AN: 152108 Hom.: 35336 Cov.: 33 AF XY: 0.683 AC XY: 50791 AN XY: 74366

African (AFR) AF: 0.557 AC: 23101 AN: 41452

American (AMR) AF: 0.694 AC: 10616 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2700 AN: 3470

East Asian (EAS) AF: 0.660 AC: 3416 AN: 5172

South Asian (SAS) AF: 0.738 AC: 3559 AN: 4822

European-Finnish (FIN) AF: 0.800 AC: 8481 AN: 10596

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48790 AN: 67988

Other (OTH) AF: 0.686 AC: 1452 AN: 2116

Alfa AF: 0.702 Hom.: 86888

Bravo AF: 0.663

Asia WGS AF: 0.678 AC: 2360 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.0090
DANN	Benign	0.46
PhyloP100		-1.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2036844;

hg19: chr5-126112153;