chr6-69794404-G-A

Variant names:

• chr6-69794404-G-A
• rs9354890
• NM_018368.4:c.69+2409C>T

Variant summary

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

The NM_018368.4(LMBRD1):​c.69+2409C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,066 control chromosomes in the GnomAD database, including 9,955 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 (9955 hom., cov: 33)
• Consequence: LMBRD1 NM_018368.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• 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: 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=-0.92).
• 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.69+2409C>T		intron_variant	Intron 1 of 15	ENST00000649934.3	NP_060838.3
LMBRD1	NM_001363722.2	c.-151+1890C>T		intron_variant	Intron 1 of 15		NP_001350651.1
LMBRD1	NM_001367271.1	c.-151+2010C>T		intron_variant	Intron 1 of 15		NP_001354200.1
LMBRD1	NM_001367272.1	c.-151+2014C>T		intron_variant	Intron 1 of 15		NP_001354201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3	c.69+2409C>T		intron_variant	Intron 1 of 15		NM_018368.4	ENSP00000497690.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52419 AN: 151948 Hom.: 9949 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.345 AC: 52441 AN: 152066 Hom.: 9955 Cov.: 33 AF XY: 0.345 AC XY: 25622 AN XY: 74346

African (AFR) AF: 0.182 AC: 7563 AN: 41480

American (AMR) AF: 0.385 AC: 5880 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3466

East Asian (EAS) AF: 0.544 AC: 2815 AN: 5176

South Asian (SAS) AF: 0.444 AC: 2143 AN: 4822

European-Finnish (FIN) AF: 0.340 AC: 3594 AN: 10568

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.406 AC: 27613 AN: 67950

Other (OTH) AF: 0.378 AC: 798 AN: 2112

Alfa AF: 0.362 Hom.: 1787

Bravo AF: 0.339

Asia WGS AF: 0.473 AC: 1648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.5
DANN	Benign	0.82
PhyloP100		-1.4
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: rs9354890; hg19: chr6-70504296; COSMIC: COSV65299757; COSMIC: COSV65299757;