6-69856377-A-G

Variant names:

• chr6-69856377-A-G
• rs2502570
• ENST00000647964.1:c.-326+10831T>C

Variant summary

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

The ENST00000647964.1(LMBRD1):​c.-326+10831T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,024 control chromosomes in the GnomAD database, including 35,174 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 0.68 (35174 hom., cov: 31)
• Consequence: LMBRD1 ENST00000647964.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.715 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.-326+10831T>C		intron	N/A	ENSP00000496784.1	Q9NUN5-3
	LMBRD1	ENST00000648394.1		c.-151+10094T>C		intron	N/A	ENSP00000497302.1	Q9NUN5-3
	LMBRD1	ENST00000649028.1		c.-215+10094T>C		intron	N/A	ENSP00000498034.1	Q9NUN5-3

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103335 AN: 151906 Hom.: 35126 Cov.: 31

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.680 AC: 103438 AN: 152024 Hom.: 35174 Cov.: 31 AF XY: 0.684 AC XY: 50869 AN XY: 74330

African (AFR) AF: 0.669 AC: 27765 AN: 41486

American (AMR) AF: 0.726 AC: 11080 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2396 AN: 3464

East Asian (EAS) AF: 0.704 AC: 3637 AN: 5166

South Asian (SAS) AF: 0.682 AC: 3291 AN: 4822

European-Finnish (FIN) AF: 0.692 AC: 7329 AN: 10586

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.674 AC: 45783 AN: 67926

Other (OTH) AF: 0.711 AC: 1501 AN: 2112

Alfa AF: 0.681 Hom.: 59108

Bravo AF: 0.683

Asia WGS AF: 0.732 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.4
DANN	Benign	0.65
PhyloP100		0.42

Splicing

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

Other links and lift over

dbSNP: rs2502570; hg19: chr6-70566269;