rs267766

Variant names:

• chr5-36143290-C-T
• rs267766
• NM_001007527.2:c.60G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001007527.2(LMBRD2):​c.60G>A​(p.Leu20Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,610,600 control chromosomes in the GnomAD database, including 134,219 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 0.40 (12448 hom., cov: 32)
  • Exomes 𝑓: 0.40 (121771 hom.)
• Consequence: LMBRD2 NM_001007527.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 22 publications found

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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 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

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=-0.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMBRD2	NM_001007527.2	c.60G>A	p.Leu20Leu	synonymous_variant	Exon 2 of 18	ENST00000296603.5	NP_001007528.1
LMBRD2	XM_011514162.3	c.60G>A	p.Leu20Leu	synonymous_variant	Exon 2 of 18		XP_011512464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBRD2	ENST00000296603.5	c.60G>A	p.Leu20Leu	synonymous_variant	Exon 2 of 18	1	NM_001007527.2	ENSP00000296603.4

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60894 AN: 151854 Hom.: 12436 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.398

GnomAD2 exomes AF: 0.373 AC: 93392 AN: 250530 AF XY: 0.373

Gnomad AFR exome AF: 0.431

Gnomad AMR exome AF: 0.262

Gnomad ASJ exome AF: 0.310

Gnomad EAS exome AF: 0.222

Gnomad FIN exome AF: 0.474

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.375

GnomAD4 exome AF: 0.405 AC: 590364 AN: 1458628 Hom.: 121771 Cov.: 31 AF XY: 0.403 AC XY: 292221 AN XY: 725802

African (AFR) AF: 0.423 AC: 14128 AN: 33380

American (AMR) AF: 0.270 AC: 12044 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 8063 AN: 26090

East Asian (EAS) AF: 0.236 AC: 9338 AN: 39616

South Asian (SAS) AF: 0.326 AC: 28062 AN: 86038

European-Finnish (FIN) AF: 0.469 AC: 25043 AN: 53386

Middle Eastern (MID) AF: 0.393 AC: 2266 AN: 5760

European-Non Finnish (NFE) AF: 0.422 AC: 467860 AN: 1109500

Other (OTH) AF: 0.391 AC: 23560 AN: 60272

GnomAD4 genome AF: 0.401 AC: 60939 AN: 151972 Hom.: 12448 Cov.: 32 AF XY: 0.399 AC XY: 29664 AN XY: 74262

African (AFR) AF: 0.428 AC: 17715 AN: 41432

American (AMR) AF: 0.313 AC: 4777 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1061 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1157 AN: 5168

South Asian (SAS) AF: 0.321 AC: 1549 AN: 4822

European-Finnish (FIN) AF: 0.475 AC: 5015 AN: 10556

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.418 AC: 28373 AN: 67942

Other (OTH) AF: 0.395 AC: 834 AN: 2112

Alfa AF: 0.404 Hom.: 18057

Bravo AF: 0.391

Asia WGS AF: 0.313 AC: 1086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	4.8
DANN	Benign	0.77
PhyloP100		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=93/7	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: rs267766; hg19: chr5-36143392; COSMIC: COSV56949104; COSMIC: COSV56949104;