rs7741758

Positions:

• chr6-69702488-A-C
• chr6-69702488-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018368.4(LMBRD1):​c.916-535T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,800 control chromosomes in the GnomAD database, including 10,439 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 (10439 hom., cov: 31)
• Consequence: LMBRD1 NM_018368.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• 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/exons	MANE	Protein	UniProt
LMBRD1	NM_018368.4	c.916-535T>G		intron_variant		ENST00000649934.3	NP_060838.3
LMBRD1	NM_001363722.2	c.697-535T>G		intron_variant			NP_001350651.1
LMBRD1	NM_001367271.1	c.697-535T>G		intron_variant			NP_001354200.1
LMBRD1	NM_001367272.1	c.697-535T>G		intron_variant			NP_001354201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3	c.916-535T>G		intron_variant			NM_018368.4	ENSP00000497690.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54657 AN: 151682 Hom.: 10432 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.360 AC: 54684 AN: 151800 Hom.: 10439 Cov.: 31 AF XY: 0.359 AC XY: 26658 AN XY: 74174

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.387

Alfa AF: 0.379 Hom.: 1667

Bravo AF: 0.357

Asia WGS AF: 0.475 AC: 1649 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs7741758; hg19: chr6-70412380;