Variant chr6-69701547-T-TA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

LMBRD1 (HGNC:):

LMBRD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 225404.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=3}.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
LMBRD1	NM_018368.4 linkuse as main transcript	c.981-3dupT	splice_region_variant, intron_variant	ENST00000649934.3	NP_060838.3	Q9NUN5-1
LMBRD1	NM_001363722.2 linkuse as main transcript	c.762-3dupT	splice_region_variant, intron_variant		NP_001350651.1
LMBRD1	NM_001367271.1 linkuse as main transcript	c.762-3dupT	splice_region_variant, intron_variant		NP_001354200.1
LMBRD1	NM_001367272.1 linkuse as main transcript	c.762-3dupT	splice_region_variant, intron_variant		NP_001354201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3 linkuse as main transcript	c.981-3dupT		splice_region_variant, intron_variant			NM_018368.4	ENSP00000497690.1		Q9NUN5-1

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

GnomAD3 exomes

AF:

0.0121

AC:

2781

AN:

229438

Hom.:

AF XY:

0.0124

AC XY:

1545

AN XY:

124620

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 SAS exome

AF:

0.0171

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

Gnomad4 AFR exome

AF:

0.000661

Gnomad4 AMR exome

AF:

0.000276

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0897

Gnomad4 SAS exome

AF:

0.0157

Gnomad4 FIN exome

AF:

0.0274

Gnomad4 NFE exome

AF:

0.00267

Gnomad4 OTH exome

AF:

0.00910

GnomAD4 genome

AF:

0.00708

AC:

1073

AN:

151586

Hom.:

Cov.:

AF XY:

0.00922

AC XY:

683

AN XY:

74080

show subpopulations

Gnomad4 AFR

AF:

0.00109

Gnomad4 AMR

AF:

0.000723

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0790

Gnomad4 SAS

AF:

0.0183

Gnomad4 FIN

AF:

0.0303

Gnomad4 NFE

AF:

0.00293

Gnomad4 OTH

AF:

0.00191

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 21, 2023	- -

Donnai-Barrow syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

reference population

Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center

Mar 18, 2016

- -

Disorders of Intracellular Cobalamin Metabolism

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over