6-69718308-C-T

Variant names:

• chr6-69718308-C-T
• rs9351772
• NM_018368.4:c.762+648G>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.762+648G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,866 control chromosomes in the GnomAD database, including 9,714 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 0.34 (9714 hom., cov: 32)
• Consequence: LMBRD1 NM_018368.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971
• 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: 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=-0.88).
• 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.762+648G>A		intron_variant	Intron 8 of 15	ENST00000649934.3	NP_060838.3
LMBRD1	NM_001363722.2	c.543+648G>A		intron_variant	Intron 8 of 15		NP_001350651.1
LMBRD1	NM_001367271.1	c.543+648G>A		intron_variant	Intron 8 of 15		NP_001354200.1
LMBRD1	NM_001367272.1	c.543+648G>A		intron_variant	Intron 8 of 15		NP_001354201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3	c.762+648G>A		intron_variant	Intron 8 of 15		NM_018368.4	ENSP00000497690.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51247 AN: 151748 Hom.: 9709 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.338 AC: 51269 AN: 151866 Hom.: 9714 Cov.: 32 AF XY: 0.338 AC XY: 25075 AN XY: 74236

African (AFR) AF: 0.160 AC: 6627 AN: 41448

American (AMR) AF: 0.379 AC: 5776 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1497 AN: 3464

East Asian (EAS) AF: 0.544 AC: 2808 AN: 5166

South Asian (SAS) AF: 0.444 AC: 2140 AN: 4820

European-Finnish (FIN) AF: 0.340 AC: 3565 AN: 10486

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27573 AN: 67928

Other (OTH) AF: 0.373 AC: 786 AN: 2110

Alfa AF: 0.358 Hom.: 1793

Bravo AF: 0.330

Asia WGS AF: 0.470 AC: 1633 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.53
PhyloP100		-0.97
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: rs9351772; hg19: chr6-70428200; COSMIC: COSV65299345;