rs267766

Positions:

• chr5-36143290-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LMBRD2	NM_001007527.2	c.60G>A	p.Leu20Leu	synonymous_variant	2/18	ENST00000296603.5	NP_001007528.1
LMBRD2	XM_011514162.3	c.60G>A	p.Leu20Leu	synonymous_variant	2/18		XP_011512464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMBRD2	ENST00000296603.5	c.60G>A	p.Leu20Leu	synonymous_variant	2/18	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

GnomAD3 exomes AF: 0.373 AC: 93392 AN: 250530 Hom.: 18341 AF XY: 0.373 AC XY: 50552 AN XY: 135428

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 SAS exome AF: 0.324

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

Gnomad4 AFR exome AF: 0.423

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.309

Gnomad4 EAS exome AF: 0.236

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.391

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

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.395

Alfa AF: 0.405 Hom.: 14413

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs267766; hg19: chr5-36143392; COSMIC: COSV56949104; COSMIC: COSV56949104;