6-69677734-A-T

Position:

• chr6-69677734-A-T

Variant summary

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

The NM_018368.4(LMBRD1):​c.1418-1193T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,828 control chromosomes in the GnomAD database, including 17,981 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 0.48 (17981 hom., cov: 31)
• Consequence: LMBRD1 NM_018368.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25

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 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMBRD1	NM_018368.4	c.1418-1193T>A		intron_variant		ENST00000649934.3	NP_060838.3
LMBRD1	NM_001363722.2	c.1199-1193T>A		intron_variant			NP_001350651.1
LMBRD1	NM_001367271.1	c.1199-1193T>A		intron_variant			NP_001354200.1
LMBRD1	NM_001367272.1	c.1199-1193T>A		intron_variant			NP_001354201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMBRD1	ENST00000649934.3	c.1418-1193T>A		intron_variant			NM_018368.4	ENSP00000497690.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72559 AN: 151710 Hom.: 17953 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.478 AC: 72632 AN: 151828 Hom.: 17981 Cov.: 31 AF XY: 0.474 AC XY: 35169 AN XY: 74182

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.447

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.481

Alfa AF: 0.453 Hom.: 1975

Bravo AF: 0.487

Asia WGS AF: 0.597 AC: 2077 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	0.31
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9294848; hg19: chr6-70387626;