dbSNP rs267759: LMBRD2:c.369-77T>C (chr5-36137518-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001007527.2(LMBRD2):c.369-77T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 902,712 control chromosomes in the GnomAD database, including 419,145 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 0.94 ( 67843 hom., cov: 32)

Exomes 𝑓: 0.96 ( 351302 hom. )

Consequence

LMBRD2
NM_001007527.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.499

Publications

15 publications found

Variant links:

Genes affected

LMBRD2 (HGNC:25287): (LMBR1 domain containing 2) Involved in adrenergic receptor signaling pathway. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

LMBRD2 Gene-Disease associations (from GenCC):

developmental delay with variable neurologic and brain abnormalities
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
neurodevelopmental disorder with microcephaly and dysmorphic facies
Inheritance: AD Classification: MODERATE Submitted by: Franklin by Genoox
complex neurodevelopmental disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

LMBRD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007527.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMBRD2	NM_001007527.2	MANE Select	c.369-77T>C		intron	N/A	NP_001007528.1	Q68DH5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LMBRD2	ENST00000296603.5	TSL:1 MANE Select	c.369-77T>C	intron	N/A	ENSP00000296603.4	Q68DH5
LMBRD2	ENST00000885486.1		c.369-77T>C	intron	N/A	ENSP00000555545.1
LMBRD2	ENST00000885487.1		c.369-77T>C	intron	N/A	ENSP00000555546.1

Frequencies

GnomAD3 genomes

AF:

0.941

AC:

143231

AN:

152182

Hom.:

67792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.900

Gnomad AMI

AF:

0.999

Gnomad AMR

AF:

0.873

Gnomad ASJ

AF:

0.969

Gnomad EAS

AF:

0.713

Gnomad SAS

AF:

0.966

Gnomad FIN

AF:

0.984

Gnomad MID

AF:

0.959

Gnomad NFE

AF:

0.988

Gnomad OTH

AF:

0.940

GnomAD4 exome

AF:

0.965

AC:

724074

AN:

750412

Hom.:

351302

AF XY:

0.966

AC XY:

365789

AN XY:

378618

show subpopulations

African (AFR)

AF:

0.899

AC:

16959

AN:

18866

American (AMR)

AF:

0.824

AC:

19210

AN:

23324

Ashkenazi Jewish (ASJ)

AF:

0.965

AC:

14291

AN:

14802

East Asian (EAS)

AF:

0.682

AC:

23297

AN:

34174

South Asian (SAS)

AF:

0.966

AC:

30636

AN:

31724

European-Finnish (FIN)

AF:

0.984

AC:

40312

AN:

40960

Middle Eastern (MID)

AF:

0.960

AC:

2416

AN:

2516

European-Non Finnish (NFE)

AF:

0.990

AC:

545048

AN:

550732

Other (OTH)

AF:

0.958

AC:

31905

AN:

33314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1063

2126

3189

4252

5315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9588

19176

28764

38352

47940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.941

AC:

143333

AN:

152300

Hom.:

67843

Cov.:

AF XY:

0.939

AC XY:

69885

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.900

AC:

37416

AN:

41566

American (AMR)

AF:

0.872

AC:

13328

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.969

AC:

3365

AN:

3472

East Asian (EAS)

AF:

0.713

AC:

3684

AN:

5168

South Asian (SAS)

AF:

0.967

AC:

4662

AN:

4820

European-Finnish (FIN)

AF:

0.984

AC:

10452

AN:

10622

Middle Eastern (MID)

AF:

0.956

AC:

281

AN:

294

European-Non Finnish (NFE)

AF:

0.988

AC:

67249

AN:

68042

Other (OTH)

AF:

0.940

AC:

1985

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

405

809

1214

1618

2023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.964

Hom.:

219533

Bravo

AF:

0.928

Asia WGS

AF:

0.867

AC:

3011

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.69

(source)

DANN

Benign

0.50

PhyloP100

0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over