chr6-69713759-G-A

Variant names:

• chr6-69713759-G-A
• rs34327883
• NM_018368.4:c.801C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018368.4(LMBRD1):​c.801C>T​(p.Arg267Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,524 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (39 hom.)
• Consequence: LMBRD1 NM_018368.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.16
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 6-69713759-G-A is Benign according to our data. Variant chr6-69713759-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 357775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.16 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0103 (1572/152136) while in subpopulation AFR AF = 0.0364 (1512/41518). AF 95% confidence interval is 0.0349. There are 32 homozygotes in GnomAd4. There are 710 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018368.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMBRD1	NM_018368.4	MANE Select	c.801C>T	p.Arg267Arg	synonymous	Exon 9 of 16	NP_060838.3
	LMBRD1	NM_001363722.2		c.582C>T	p.Arg194Arg	synonymous	Exon 9 of 16	NP_001350651.1
	LMBRD1	NM_001367271.1		c.582C>T	p.Arg194Arg	synonymous	Exon 9 of 16	NP_001354200.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMBRD1	ENST00000649934.3	MANE Select	c.801C>T	p.Arg267Arg	synonymous	Exon 9 of 16	ENSP00000497690.1
	LMBRD1	ENST00000370570.6	TSL:1	c.582C>T	p.Arg194Arg	synonymous	Exon 9 of 16	ENSP00000359602.1
	LMBRD1	ENST00000649011.1		c.867C>T	p.Arg289Arg	synonymous	Exon 10 of 17	ENSP00000497575.1

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1566 AN: 152018 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00299 AC: 749 AN: 250920 AF XY: 0.00199

Gnomad AFR exome AF: 0.0406

Gnomad AMR exome AF: 0.00177

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000970

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00113 AC: 1647 AN: 1461388 Hom.: 39 Cov.: 32 AF XY: 0.000928 AC XY: 675 AN XY: 727000

African (AFR) AF: 0.0396 AC: 1324 AN: 33442

American (AMR) AF: 0.00195 AC: 87 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5762

European-Non Finnish (NFE) AF: 0.0000648 AC: 72 AN: 1111682

Other (OTH) AF: 0.00219 AC: 132 AN: 60382

GnomAD4 genome AF: 0.0103 AC: 1572 AN: 152136 Hom.: 32 Cov.: 32 AF XY: 0.00955 AC XY: 710 AN XY: 74374

African (AFR) AF: 0.0364 AC: 1512 AN: 41518

American (AMR) AF: 0.00236 AC: 36 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67988

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

Alfa AF: 0.00653 Hom.: 6

Bravo AF: 0.0114

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Methylmalonic aciduria and homocystinuria type cblF (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.56
DANN	Benign	0.59
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism

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: rs34327883; hg19: chr6-70423651;