rs991974

Variant names:

• chr6-69771375-G-T
• rs991974
• NM_018368.4:c.307+9119C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018368.4(LMBRD1):​c.307+9119C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,154 control chromosomes in the GnomAD database, including 2,687 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 0.11 (2687 hom., cov: 33)
• Consequence: LMBRD1 NM_018368.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 4 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]

LMBRD1 Gene-Disease associations (from GenCC):

• methylmalonic aciduria and homocystinuria type cblF

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMBRD1	NM_018368.4	c.307+9119C>A		intron_variant	Intron 3 of 15	ENST00000649934.3	NP_060838.3
LMBRD1	NM_001363722.2	c.88+9119C>A		intron_variant	Intron 3 of 15		NP_001350651.1
LMBRD1	NM_001367271.1	c.88+9119C>A		intron_variant	Intron 3 of 15		NP_001354200.1
LMBRD1	NM_001367272.1	c.88+9119C>A		intron_variant	Intron 3 of 15		NP_001354201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3	c.307+9119C>A		intron_variant	Intron 3 of 15		NM_018368.4	ENSP00000497690.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17043 AN: 152036 Hom.: 2680 Cov.: 33

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0537

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.0661

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0811

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

GnomAD4 genome AF: 0.112 AC: 17094 AN: 152154 Hom.: 2687 Cov.: 33 AF XY: 0.109 AC XY: 8103 AN XY: 74430

African (AFR) AF: 0.351 AC: 14556 AN: 41470

American (AMR) AF: 0.0536 AC: 820 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.0532 AC: 276 AN: 5184

South Asian (SAS) AF: 0.0659 AC: 318 AN: 4824

European-Finnish (FIN) AF: 0.0155 AC: 164 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 762 AN: 67992

Other (OTH) AF: 0.0850 AC: 179 AN: 2106

Alfa AF: 0.0374 Hom.: 300

Bravo AF: 0.124

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.57
PhyloP100		-0.091
Mutation Taster		=100/0	polymorphism (auto)

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: rs991974; hg19: chr6-70481267;