6-69856377-A-G

Variant names:

• chr6-69856377-A-G
• rs2502570
• ENST00000647964.1:c.-326+10831T>C

Variant summary

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

The ENST00000647964.1(LMBRD1):​c.-326+10831T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,024 control chromosomes in the GnomAD database, including 35,174 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 0.68 (35174 hom., cov: 31)
• Consequence: LMBRD1 ENST00000647964.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.715 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.-326+10831T>C		intron_variant	Intron 1 of 16			ENSP00000496784.1
LMBRD1	ENST00000648394.1	c.-151+10094T>C		intron_variant	Intron 1 of 15			ENSP00000497302.1
LMBRD1	ENST00000649028.1	c.-215+10094T>C		intron_variant	Intron 1 of 16			ENSP00000498034.1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103335 AN: 151906 Hom.: 35126 Cov.: 31

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.680 AC: 103438 AN: 152024 Hom.: 35174 Cov.: 31 AF XY: 0.684 AC XY: 50869 AN XY: 74330

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.726

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.711

Alfa AF: 0.680 Hom.: 46318

Bravo AF: 0.683

Asia WGS AF: 0.732 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.4
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2502570; hg19: chr6-70566269;