chr6-69746786-G-T

Variant names:

• chr6-69746786-G-T
• rs10498869
• NM_018368.4:c.473+2555C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018368.4(LMBRD1):​c.473+2555C>A variant causes a intron change. The variant allele was found at a frequency of 0.0000552 in 18,112 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: LMBRD1 NM_018368.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.08
• Publications: 0 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]

GAPDHP42 (HGNC:37799): (glyceraldehyde 3 phosphate dehydrogenase pseudogene 42)

LOC124901337 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMBRD1	NM_018368.4	c.473+2555C>A		intron_variant	Intron 5 of 15	ENST00000649934.3	NP_060838.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3	c.473+2555C>A		intron_variant	Intron 5 of 15		NM_018368.4	ENSP00000497690.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.0000552 AC: 1 AN: 18112 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10696

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 676

American (AMR) AF: 0.00 AC: 0 AN: 2076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 310

East Asian (EAS) AF: 0.00 AC: 0 AN: 1560

South Asian (SAS) AF: 0.000715 AC: 1 AN: 1398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 36

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 9874

Other (OTH) AF: 0.00 AC: 0 AN: 864

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.9
DANN	Benign	0.73
PhyloP100		5.1

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: rs10498869; hg19: chr6-70456678;