6-69747737-C-T

Variant names:

• chr6-69747737-C-T
• rs9294851
• NM_018368.4:c.473+1604G>A

Variant summary

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

The NM_018368.4(LMBRD1):​c.473+1604G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,026 control chromosomes in the GnomAD database, including 10,470 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 (10470 hom., cov: 32)
• Consequence: LMBRD1 NM_018368.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 7 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen, Orphanet

LOC124901337 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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 rank	MANE	Protein	UniProt
LMBRD1	NM_018368.4	c.473+1604G>A		intron_variant	Intron 5 of 15	ENST00000649934.3	NP_060838.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3	c.473+1604G>A		intron_variant	Intron 5 of 15		NM_018368.4	ENSP00000497690.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54785 AN: 151908 Hom.: 10463 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: 0.542

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

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

GnomAD4 genome AF: 0.361 AC: 54812 AN: 152026 Hom.: 10470 Cov.: 32 AF XY: 0.360 AC XY: 26726 AN XY: 74332

African (AFR) AF: 0.237 AC: 9822 AN: 41484

American (AMR) AF: 0.392 AC: 5984 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3466

East Asian (EAS) AF: 0.543 AC: 2799 AN: 5154

South Asian (SAS) AF: 0.444 AC: 2143 AN: 4824

European-Finnish (FIN) AF: 0.339 AC: 3586 AN: 10568

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

European-Non Finnish (NFE) AF: 0.407 AC: 27623 AN: 67932

Other (OTH) AF: 0.387 AC: 815 AN: 2108

Alfa AF: 0.392 Hom.: 6543

Bravo AF: 0.357

Asia WGS AF: 0.476 AC: 1657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.71
PhyloP100		-1.1
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: rs9294851; hg19: chr6-70457629;