Variant chr6-69713847-A-G 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.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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	MANE	Protein
LMBRD1	NM_018368.4 linkuse as main transcript	c.763-50T>C	intron_variant	ENST00000649934.3	NP_060838.3
LMBRD1	NM_001363722.2 linkuse as main transcript	c.544-50T>C	intron_variant		NP_001350651.1
LMBRD1	NM_001367271.1 linkuse as main transcript	c.544-50T>C	intron_variant		NP_001354200.1
LMBRD1	NM_001367272.1 linkuse as main transcript	c.544-50T>C	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.763-50T>C		intron_variant			NM_018368.4	ENSP00000497690	P2	Q9NUN5-1

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

GnomAD3 exomes

AF:

0.404

AC:

98168

AN:

243216

Hom.:

20268

AF XY:

0.409

AC XY:

53950

AN XY:

131836

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 SAS exome

AF:

0.444

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

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.389

Gnomad4 ASJ exome

AF:

0.446

Gnomad4 EAS exome

AF:

0.546

Gnomad4 SAS exome

AF:

0.444

Gnomad4 FIN exome

AF:

0.349

Gnomad4 NFE exome

AF:

0.399

Gnomad4 OTH exome

AF:

0.405

GnomAD4 genome

AF:

0.360

AC:

54750

AN:

151926

Hom.:

10455

Cov.:

AF XY:

0.359

AC XY:

26679

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.237

Gnomad4 AMR

AF:

0.391

Gnomad4 ASJ

AF:

0.443

Gnomad4 EAS

AF:

0.542

Gnomad4 SAS

AF:

0.445

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.407

Gnomad4 OTH

AF:

0.387

Alfa

AF:

0.389

Hom.:

2586

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

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.4

DANN

Benign

0.48

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