chr6-69680240-T-G

Variant names:

• chr6-69680240-T-G
• rs4706271
• NM_018368.4:c.1418-3699A>C

Variant summary

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

The NM_018368.4(LMBRD1):​c.1418-3699A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,042 control chromosomes in the GnomAD database, including 10,545 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 (10545 hom., cov: 32)
• Consequence: LMBRD1 NM_018368.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMBRD1	NM_018368.4	c.1418-3699A>C		intron_variant	Intron 14 of 15	ENST00000649934.3	NP_060838.3
LMBRD1	NM_001363722.2	c.1199-3699A>C		intron_variant	Intron 14 of 15		NP_001350651.1
LMBRD1	NM_001367271.1	c.1199-3699A>C		intron_variant	Intron 14 of 15		NP_001354200.1
LMBRD1	NM_001367272.1	c.1199-3699A>C		intron_variant	Intron 14 of 15		NP_001354201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3	c.1418-3699A>C		intron_variant	Intron 14 of 15		NM_018368.4	ENSP00000497690.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54999 AN: 151924 Hom.: 10538 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: 0.543

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.362 AC: 55026 AN: 152042 Hom.: 10545 Cov.: 32 AF XY: 0.361 AC XY: 26812 AN XY: 74328

African (AFR) AF: 0.237 AC: 9834 AN: 41496

American (AMR) AF: 0.391 AC: 5973 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1535 AN: 3466

East Asian (EAS) AF: 0.544 AC: 2810 AN: 5166

South Asian (SAS) AF: 0.446 AC: 2151 AN: 4820

European-Finnish (FIN) AF: 0.342 AC: 3620 AN: 10582

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

European-Non Finnish (NFE) AF: 0.409 AC: 27781 AN: 67932

Other (OTH) AF: 0.388 AC: 819 AN: 2110

Alfa AF: 0.290 Hom.: 1006

Bravo AF: 0.358

Asia WGS AF: 0.477 AC: 1659 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		0.42
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: rs4706271; hg19: chr6-70390132; COSMIC: COSV65299174;