dbSNP rs2305837: LMBRD1:c.763-50T>C (chr6-69713847-A-G) – ACMG Classification: Benign (-20 pts)

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

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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet

LMBRD1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_018368.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018368.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LMBRD1	NM_018368.4	MANE Select	c.763-50T>C	intron	N/A	NP_060838.3
LMBRD1	NM_001363722.2		c.544-50T>C	intron	N/A	NP_001350651.1	Q9NUN5-3
LMBRD1	NM_001367271.1		c.544-50T>C	intron	N/A	NP_001354200.1	Q9NUN5-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LMBRD1	ENST00000649934.3	MANE Select	c.763-50T>C	intron	N/A	ENSP00000497690.1	Q9NUN5-1
LMBRD1	ENST00000370570.6	TSL:1	c.544-50T>C	intron	N/A	ENSP00000359602.1	Q9NUN5-3
LMBRD1	ENST00000875440.1		c.883-50T>C	intron	N/A	ENSP00000545499.1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54723

AN:

151808

Hom.:

10448

Cov.:

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.:

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

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

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.:

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

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

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.4

(source)

DANN

Benign

0.48

PhyloP100

1.8

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over