6-69677734-A-T

Variant names:

• chr6-69677734-A-T
• rs9294848
• NM_018368.4:c.1418-1193T>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.1418-1193T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,828 control chromosomes in the GnomAD database, including 17,981 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 0.48 (17981 hom., cov: 31)
• Consequence: LMBRD1 NM_018368.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.592 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.1418-1193T>A		intron	N/A	NP_060838.3
	LMBRD1	NM_001363722.2		c.1199-1193T>A		intron	N/A	NP_001350651.1	Q9NUN5-3
	LMBRD1	NM_001367271.1		c.1199-1193T>A		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.1418-1193T>A		intron	N/A	ENSP00000497690.1	Q9NUN5-1
	LMBRD1	ENST00000370570.6	TSL:1	c.1199-1193T>A		intron	N/A	ENSP00000359602.1	Q9NUN5-3
	LMBRD1	ENST00000875440.1		c.1538-1193T>A		intron	N/A	ENSP00000545499.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72559 AN: 151710 Hom.: 17953 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.478 AC: 72632 AN: 151828 Hom.: 17981 Cov.: 31 AF XY: 0.474 AC XY: 35169 AN XY: 74182

African (AFR) AF: 0.598 AC: 24761 AN: 41400

American (AMR) AF: 0.452 AC: 6875 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1546 AN: 3462

East Asian (EAS) AF: 0.597 AC: 3083 AN: 5162

South Asian (SAS) AF: 0.512 AC: 2460 AN: 4808

European-Finnish (FIN) AF: 0.359 AC: 3780 AN: 10534

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28605 AN: 67934

Other (OTH) AF: 0.481 AC: 1012 AN: 2106

Alfa AF: 0.453 Hom.: 1975

Bravo AF: 0.487

Asia WGS AF: 0.597 AC: 2077 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	0.31
DANN	Benign	0.49
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9294848; hg19: chr6-70387626;