6-69701547-TA-TAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_018368.4(LMBRD1):c.981-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00693 in 1,541,856 control chromosomes in the GnomAD database, including 238 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0071 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 216 hom. )

Consequence

LMBRD1
NM_018368.4 splice_region, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: -0.138

Publications

1 publications found

Variant links:

Genes affected

LMBRD1 (HGNC:23038): (LMBR1 domain containing 1) This gene encodes a lysosomal membrane protein that may be involved in the transport and metabolism of cobalamin. This protein also interacts with the large form of the hepatitis delta antigen and may be required for the nucleocytoplasmic shuttling of the hepatitis delta virus. Mutations in this gene are associated with the vitamin B12 metabolism disorder termed, homocystinuria-megaloblastic anemia complementation type F.[provided by RefSeq, Oct 2009]

LMBRD1 Gene-Disease associations (from GenCC):

methylmalonic aciduria and homocystinuria type cblF
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen, Orphanet

LMBRD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 6-69701547-T-TA is Benign according to our data. Variant chr6-69701547-T-TA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 225404.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
LMBRD1	NM_018368.4 link	c.981-3dupT	splice_region_variant, intron_variant	Intron 10 of 15	ENST00000649934.3	NP_060838.3
LMBRD1	NM_001363722.2 link	c.762-3dupT	splice_region_variant, intron_variant	Intron 10 of 15		NP_001350651.1
LMBRD1	NM_001367271.1 link	c.762-3dupT	splice_region_variant, intron_variant	Intron 10 of 15		NP_001354200.1
LMBRD1	NM_001367272.1 link	c.762-3dupT	splice_region_variant, intron_variant	Intron 10 of 15		NP_001354201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3 link	c.981-3_981-2insT		splice_region_variant, intron_variant	Intron 10 of 15		NM_018368.4	ENSP00000497690.1

Frequencies

GnomAD3 genomes

AF:

0.00709

AC:

1074

AN:

151468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000724

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0791

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.0303

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00292

Gnomad OTH

AF:

0.00193

GnomAD2 exomes

AF:

0.0121

AC:

2781

AN:

229438

AF XY:

0.0124

show subpopulations

Gnomad AFR exome

AF:

0.000958

Gnomad AMR exome

AF:

0.000279

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0734

Gnomad FIN exome

AF:

0.0272

Gnomad NFE exome

AF:

0.00372

Gnomad OTH exome

AF:

0.0107

GnomAD4 exome

AF:

0.00691

AC:

9611

AN:

1390270

Hom.:

216

Cov.:

AF XY:

0.00704

AC XY:

4895

AN XY:

694824

show subpopulations

African (AFR)

AF:

0.000661

AC:

AN:

31758

American (AMR)

AF:

0.000276

AC:

AN:

43426

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25146

East Asian (EAS)

AF:

0.0897

AC:

3479

AN:

38776

South Asian (SAS)

AF:

0.0157

AC:

1309

AN:

83154

European-Finnish (FIN)

AF:

0.0274

AC:

1440

AN:

52602

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5346

European-Non Finnish (NFE)

AF:

0.00267

AC:

2812

AN:

1052340

Other (OTH)

AF:

0.00910

AC:

525

AN:

57722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

439

878

1316

1755

2194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

146

292

438

584

730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00708

AC:

1073

AN:

151586

Hom.:

Cov.:

AF XY:

0.00922

AC XY:

683

AN XY:

74080

show subpopulations

African (AFR)

AF:

0.00109

AC:

AN:

41432

American (AMR)

AF:

0.000723

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.0790

AC:

409

AN:

5174

South Asian (SAS)

AF:

0.0183

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0303

AC:

318

AN:

10494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00293

AC:

198

AN:

67688

Other (OTH)

AF:

0.00191

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

103

154

206

257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00288

Hom.:

Bravo

AF:

0.00426

Asia WGS

AF:

0.0390

AC:

133

AN:

3458

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Methylmalonic aciduria and homocystinuria type cblF

Benign:2

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 21, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Donnai-Barrow syndrome

Uncertain:1

Mar 18, 2016

Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:reference population

- -

Disorders of Intracellular Cobalamin Metabolism

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

May 17, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.14

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over