6-69713847-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018368.4(LMBRD1):​c.763-50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 1,599,284 control chromosomes in the GnomAD database, including 127,984 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 ( 10455 hom., cov: 32)
Exomes 𝑓: 0.40 ( 117529 hom. )

Consequence

LMBRD1
NM_018368.4 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.83

Publications

6 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 6-69713847-A-G is Benign according to our data. Variant chr6-69713847-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 261025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LMBRD1NM_018368.4 linkc.763-50T>C intron_variant Intron 8 of 15 ENST00000649934.3 NP_060838.3 Q9NUN5-1
LMBRD1NM_001363722.2 linkc.544-50T>C intron_variant Intron 8 of 15 NP_001350651.1
LMBRD1NM_001367271.1 linkc.544-50T>C intron_variant Intron 8 of 15 NP_001354200.1
LMBRD1NM_001367272.1 linkc.544-50T>C intron_variant Intron 8 of 15 NP_001354201.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LMBRD1ENST00000649934.3 linkc.763-50T>C intron_variant Intron 8 of 15 NM_018368.4 ENSP00000497690.1 Q9NUN5-1

Frequencies

GnomAD3 genomes
AF:
0.360
AC:
54723
AN:
151808
Hom.:
10448
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.237
Gnomad AMI
AF:
0.398
Gnomad AMR
AF:
0.391
Gnomad ASJ
AF:
0.443
Gnomad EAS
AF:
0.541
Gnomad SAS
AF:
0.444
Gnomad FIN
AF:
0.339
Gnomad MID
AF:
0.475
Gnomad NFE
AF:
0.407
Gnomad OTH
AF:
0.384
GnomAD2 exomes
AF:
0.404
AC:
98168
AN:
243216
AF XY:
0.409
show subpopulations
Gnomad AFR exome
AF:
0.232
Gnomad AMR exome
AF:
0.389
Gnomad ASJ exome
AF:
0.441
Gnomad EAS exome
AF:
0.552
Gnomad FIN exome
AF:
0.340
Gnomad NFE exome
AF:
0.406
Gnomad OTH exome
AF:
0.407
GnomAD4 exome
AF:
0.400
AC:
579614
AN:
1447358
Hom.:
117529
Cov.:
27
AF XY:
0.403
AC XY:
290462
AN XY:
720498
show subpopulations
African (AFR)
AF:
0.226
AC:
7511
AN:
33196
American (AMR)
AF:
0.389
AC:
17223
AN:
44228
Ashkenazi Jewish (ASJ)
AF:
0.446
AC:
11575
AN:
25970
East Asian (EAS)
AF:
0.546
AC:
21571
AN:
39512
South Asian (SAS)
AF:
0.444
AC:
38049
AN:
85720
European-Finnish (FIN)
AF:
0.349
AC:
18479
AN:
52986
Middle Eastern (MID)
AF:
0.448
AC:
2286
AN:
5100
European-Non Finnish (NFE)
AF:
0.399
AC:
438702
AN:
1100884
Other (OTH)
AF:
0.405
AC:
24218
AN:
59762
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
17778
35556
53334
71112
88890
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
13572
27144
40716
54288
67860
<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:
0.360
AC:
54750
AN:
151926
Hom.:
10455
Cov.:
32
AF XY:
0.359
AC XY:
26679
AN XY:
74238
show subpopulations
African (AFR)
AF:
0.237
AC:
9813
AN:
41486
American (AMR)
AF:
0.391
AC:
5945
AN:
15210
Ashkenazi Jewish (ASJ)
AF:
0.443
AC:
1537
AN:
3470
East Asian (EAS)
AF:
0.542
AC:
2795
AN:
5158
South Asian (SAS)
AF:
0.445
AC:
2141
AN:
4816
European-Finnish (FIN)
AF:
0.339
AC:
3579
AN:
10560
Middle Eastern (MID)
AF:
0.476
AC:
140
AN:
294
European-Non Finnish (NFE)
AF:
0.407
AC:
27621
AN:
67912
Other (OTH)
AF:
0.387
AC:
818
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
1755
3509
5264
7018
8773
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
542
1084
1626
2168
2710
<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:
0.386
Hom.:
2610
Bravo
AF:
0.357
Asia WGS
AF:
0.476
AC:
1656
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Jun 29, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
9.4
DANN
Benign
0.48
PhyloP100
1.8
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2305837; hg19: chr6-70423739; COSMIC: COSV65299324; API