rs3214021

chr6-69676428-C-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.1509+22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,599,476 control chromosomes in the GnomAD database, including 129,440 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 (10557 hom., cov: 31)
  • Exomes 𝑓: 0.40 (118883 hom.)
• Consequence: LMBRD1 NM_018368.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0240

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=-0.87).
• BP6: Variant 6-69676428-C-T is Benign according to our data. Variant chr6-69676428-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMBRD1	NM_018368.4	c.1509+22G>A		intron_variant		ENST00000649934.3
LMBRD1	NM_001363722.2	c.1290+22G>A		intron_variant
LMBRD1	NM_001367271.1	c.1290+22G>A		intron_variant
LMBRD1	NM_001367272.1	c.1290+22G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMBRD1	ENST00000649934.3	c.1509+22G>A		intron_variant			NM_018368.4	P2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55037 AN: 151798 Hom.: 10549 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.386

GnomAD3 exomes AF: 0.403 AC: 100647 AN: 249472 Hom.: 20940 AF XY: 0.410 AC XY: 55235 AN XY: 134874

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.389

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.550

Gnomad SAS exome AF: 0.445

Gnomad FIN exome AF: 0.342

Gnomad NFE exome AF: 0.406

Gnomad OTH exome AF: 0.406

GnomAD4 exome AF: 0.403 AC: 582655 AN: 1447558 Hom.: 118883 Cov.: 29 AF XY: 0.405 AC XY: 292179 AN XY: 721092

Gnomad4 AFR exome AF: 0.227

Gnomad4 AMR exome AF: 0.390

Gnomad4 ASJ exome AF: 0.445

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.362 AC: 55066 AN: 151918 Hom.: 10557 Cov.: 31 AF XY: 0.361 AC XY: 26819 AN XY: 74228

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.389

Alfa AF: 0.394 Hom.: 2215

Bravo AF: 0.358

Asia WGS AF: 0.476 AC: 1656 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 10, 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. -

Methylmalonic aciduria and homocystinuria type cblF Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.7
Dann	Benign	0.28

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: rs3214021; hg19: chr6-70386320; COSMIC: COSV65296527;