rs34327883

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_018368.4(LMBRD1):c.801C>T(p.Arg267Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,524 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 32 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 39 hom. )

Consequence

LMBRD1
NM_018368.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.16

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 6-69713759-G-A is Benign according to our data. Variant chr6-69713759-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 357775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.16 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1572/152136) while in subpopulation AFR AF= 0.0364 (1512/41518). AF 95% confidence interval is 0.0349. There are 32 homozygotes in gnomad4. There are 710 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMBRD1	NM_018368.4 linkuse as main transcript	c.801C>T	p.Arg267Arg	synonymous_variant	9/16	ENST00000649934.3	NP_060838.3	Q9NUN5-1
LMBRD1	NM_001363722.2 linkuse as main transcript	c.582C>T	p.Arg194Arg	synonymous_variant	9/16		NP_001350651.1
LMBRD1	NM_001367271.1 linkuse as main transcript	c.582C>T	p.Arg194Arg	synonymous_variant	9/16		NP_001354200.1
LMBRD1	NM_001367272.1 linkuse as main transcript	c.582C>T	p.Arg194Arg	synonymous_variant	9/16		NP_001354201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3 linkuse as main transcript	c.801C>T	p.Arg267Arg	synonymous_variant	9/16		NM_018368.4	ENSP00000497690.1		Q9NUN5-1

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1566

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00299

AC:

749

AN:

250920

Hom.:

AF XY:

0.00199

AC XY:

270

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.0406

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000970

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00113

AC:

1647

AN:

1461388

Hom.:

Cov.:

AF XY:

0.000928

AC XY:

675

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.0396

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000648

Gnomad4 OTH exome

AF:

0.00219

GnomAD4 genome

AF:

0.0103

AC:

1572

AN:

152136

Hom.:

Cov.:

AF XY:

0.00955

AC XY:

710

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0364

Gnomad4 AMR

AF:

0.00236

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00811

Hom.:

Bravo

AF:

0.0114

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Methylmalonic aciduria and homocystinuria type cblF

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 08, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.56

DANN

Benign

0.59

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