Variant rs3214021 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018368.4(LMBRD1):c.1509+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,599,476 control chromosomes in the GnomAD database, including 129,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10557 hom., cov: 31)

Exomes 𝑓: 0.40 ( 118883 hom. )

Consequence

LMBRD1
NM_018368.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0240

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 6-69676428-C-T is Benign according to our data. Variant chr6-69676428-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
LMBRD1	NM_018368.4 linkuse as main transcript	c.1509+22G>A	intron_variant	ENST00000649934.3	NP_060838.3
LMBRD1	NM_001363722.2 linkuse as main transcript	c.1290+22G>A	intron_variant		NP_001350651.1
LMBRD1	NM_001367271.1 linkuse as main transcript	c.1290+22G>A	intron_variant		NP_001354200.1
LMBRD1	NM_001367272.1 linkuse as main transcript	c.1290+22G>A	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.1509+22G>A		intron_variant			NM_018368.4	ENSP00000497690	P2	Q9NUN5-1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55037

AN:

151798

Hom.:

10549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.238

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.443

Gnomad EAS

AF:

0.542

Gnomad SAS

AF:

0.445

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.471

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.386

GnomAD3 exomes

AF:

0.403

AC:

100647

AN:

249472

Hom.:

20940

AF XY:

0.410

AC XY:

55235

AN XY:

134874

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.389

Gnomad ASJ exome

AF:

0.439

Gnomad EAS exome

AF:

0.550

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.406

Gnomad OTH exome

AF:

0.406

GnomAD4 exome

AF:

0.403

AC:

582655

AN:

1447558

Hom.:

118883

Cov.:

AF XY:

0.405

AC XY:

292179

AN XY:

721092

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.390

Gnomad4 ASJ exome

AF:

0.445

Gnomad4 EAS exome

AF:

0.545

Gnomad4 SAS exome

AF:

0.445

Gnomad4 FIN exome

AF:

0.352

Gnomad4 NFE exome

AF:

0.401

Gnomad4 OTH exome

AF:

0.406

GnomAD4 genome

AF:

0.362

AC:

55066

AN:

151918

Hom.:

10557

Cov.:

AF XY:

0.361

AC XY:

26819

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.238

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.443

Gnomad4 EAS

AF:

0.543

Gnomad4 SAS

AF:

0.446

Gnomad4 FIN

AF:

0.343

Gnomad4 NFE

AF:

0.409

Gnomad4 OTH

AF:

0.389

Alfa

AF:

0.394

Hom.:

2215

Bravo

AF:

0.358

Asia WGS

AF:

0.476

AC:

1656

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 10, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Methylmalonic aciduria and homocystinuria type cblF

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.7

DANN

Benign

0.28

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