rs10498869

Positions:

• chr6-69746786-G-A

Variant summary

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

The NM_018368.4(LMBRD1):​c.473+2555C>T variant causes a intron change. The variant allele was found at a frequency of 0.0636 in 170,136 control chromosomes in the GnomAD database, including 501 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 0.063 (459 hom., cov: 30)
  • Exomes 𝑓: 0.064 (42 hom.)
• Consequence: LMBRD1 NM_018368.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.08

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]

GAPDHP42 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMBRD1	NM_018368.4	c.473+2555C>T		intron_variant		ENST00000649934.3	NP_060838.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3	c.473+2555C>T		intron_variant			NM_018368.4	ENSP00000497690.1

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 9653 AN: 151968 Hom.: 458 Cov.: 30

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0824

Gnomad OTH AF: 0.0580

GnomAD4 exome AF: 0.0643 AC: 1160 AN: 18050 Hom.: 42 Cov.: 0 AF XY: 0.0638 AC XY: 681 AN XY: 10670

Gnomad4 AFR exome AF: 0.0104

Gnomad4 AMR exome AF: 0.0849

Gnomad4 ASJ exome AF: 0.0258

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0560

Gnomad4 FIN exome AF: 0.0915

Gnomad4 NFE exome AF: 0.0718

Gnomad4 OTH exome AF: 0.0731

GnomAD4 genome AF: 0.0635 AC: 9655 AN: 152086 Hom.: 459 Cov.: 30 AF XY: 0.0665 AC XY: 4942 AN XY: 74352

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.0829

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.00194

Gnomad4 SAS AF: 0.0779

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.0825

Gnomad4 OTH AF: 0.0564

Alfa AF: 0.0788 Hom.: 252

Bravo AF: 0.0553

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.5
DANN	Benign	0.73

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: rs10498869; hg19: chr6-70456678;