6-69804858-C-T

Variant names:

• chr6-69804858-C-T
• rs9364063
• ENST00000647964.1:c.-150-14386G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000647964.1(LMBRD1):​c.-150-14386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,012 control chromosomes in the GnomAD database, including 14,938 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (14938 hom., cov: 32)
• Consequence: LMBRD1 ENST00000647964.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000647964.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMBRD1	ENST00000647964.1		c.-150-14386G>A		intron	N/A	ENSP00000496784.1	Q9NUN5-3
	LMBRD1	ENST00000648394.1		c.-150-14386G>A		intron	N/A	ENSP00000497302.1	Q9NUN5-3
	LMBRD1	ENST00000649028.1		c.-150-14386G>A		intron	N/A	ENSP00000498034.1	Q9NUN5-3

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66765 AN: 151894 Hom.: 14929 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.438

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.439 AC: 66800 AN: 152012 Hom.: 14938 Cov.: 32 AF XY: 0.435 AC XY: 32352 AN XY: 74302

African (AFR) AF: 0.510 AC: 21148 AN: 41450

American (AMR) AF: 0.427 AC: 6532 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1498 AN: 3470

East Asian (EAS) AF: 0.547 AC: 2825 AN: 5160

South Asian (SAS) AF: 0.445 AC: 2143 AN: 4812

European-Finnish (FIN) AF: 0.338 AC: 3570 AN: 10552

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27661 AN: 67964

Other (OTH) AF: 0.436 AC: 923 AN: 2116

Alfa AF: 0.423 Hom.: 23339

Bravo AF: 0.446

Asia WGS AF: 0.488 AC: 1699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.34
PhyloP100		0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9364063; hg19: chr6-70514750; COSMIC: COSV69404036;