chr6-69804858-C-T

Variant names:

• chr6-69804858-C-T
• rs9364063
• ENST00000647964.1:c.-150-14386G>A

Variant summary

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

The ENST00000647964.1(LMBRD1):​c.-150-14386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 152,012 control chromosomes in the GnomAD database, including 14,938 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 0.44 (14938 hom., cov: 32)
• Consequence: LMBRD1 ENST00000647964.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.456

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000647964.1	c.-150-14386G>A		intron_variant	Intron 2 of 16			ENSP00000496784.1
LMBRD1	ENST00000648394.1	c.-150-14386G>A		intron_variant	Intron 1 of 15			ENSP00000497302.1
LMBRD1	ENST00000649028.1	c.-150-14386G>A		intron_variant	Intron 2 of 16			ENSP00000498034.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66765 AN: 151894 Hom.: 14929 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.439 AC: 66800 AN: 152012 Hom.: 14938 Cov.: 32 AF XY: 0.435 AC XY: 32352 AN XY: 74302

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.436

Alfa AF: 0.414 Hom.: 13144

Bravo AF: 0.446

Asia WGS AF: 0.488 AC: 1699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.6
DANN	Benign	0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9364063; hg19: chr6-70514750; COSMIC: COSV69404036;