rs2305837

chr6-69713847-A-Gchr6-69713847-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.83

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
LMBRD1	NM_018368.4	c.763-50T>C		intron_variant		ENST00000649934.3
LMBRD1	NM_001363722.2	c.544-50T>C		intron_variant
LMBRD1	NM_001367271.1	c.544-50T>C		intron_variant
LMBRD1	NM_001367272.1	c.544-50T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMBRD1	ENST00000649934.3	c.763-50T>C		intron_variant			NM_018368.4	P2

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54723 AN: 151808 Hom.: 10448 Cov.: 32

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

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.: 27 AF XY: 0.403 AC XY: 290462 AN XY: 720498

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.: 32 AF XY: 0.359 AC XY: 26679 AN XY: 74238

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

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

Other links and lift over

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