6-69702488-A-C

Variant names:

• chr6-69702488-A-C
• rs7741758
• NM_018368.4:c.916-535T>G

Variant summary

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

The NM_018368.4(LMBRD1):​c.916-535T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,800 control chromosomes in the GnomAD database, including 10,439 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 0.36 (10439 hom., cov: 31)
• Consequence: LMBRD1 NM_018368.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018368.4. 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
	LMBRD1	NM_018368.4	MANE Select	c.916-535T>G		intron	N/A	NP_060838.3
	LMBRD1	NM_001363722.2		c.697-535T>G		intron	N/A	NP_001350651.1	Q9NUN5-3
	LMBRD1	NM_001367271.1		c.697-535T>G		intron	N/A	NP_001354200.1	Q9NUN5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMBRD1	ENST00000649934.3	MANE Select	c.916-535T>G		intron	N/A	ENSP00000497690.1	Q9NUN5-1
	LMBRD1	ENST00000370570.6	TSL:1	c.697-535T>G		intron	N/A	ENSP00000359602.1	Q9NUN5-3
	LMBRD1	ENST00000875440.1		c.1036-535T>G		intron	N/A	ENSP00000545499.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54657 AN: 151682 Hom.: 10432 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.360 AC: 54684 AN: 151800 Hom.: 10439 Cov.: 31 AF XY: 0.359 AC XY: 26658 AN XY: 74174

African (AFR) AF: 0.236 AC: 9786 AN: 41434

American (AMR) AF: 0.391 AC: 5943 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1536 AN: 3460

East Asian (EAS) AF: 0.543 AC: 2804 AN: 5168

South Asian (SAS) AF: 0.445 AC: 2145 AN: 4818

European-Finnish (FIN) AF: 0.339 AC: 3576 AN: 10540

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27579 AN: 67872

Other (OTH) AF: 0.387 AC: 814 AN: 2104

Alfa AF: 0.374 Hom.: 1691

Bravo AF: 0.357

Asia WGS AF: 0.475 AC: 1649 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.78
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7741758; hg19: chr6-70412380;