5-36147704-C-T

Variant names:

• chr5-36147704-C-T
• rs10071838
• NM_001007527.2:c.-58+3852G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001007527.2(LMBRD2):​c.-58+3852G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,006 control chromosomes in the GnomAD database, including 8,126 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 0.31 (8126 hom., cov: 32)
• Consequence: LMBRD2 NM_001007527.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 11 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]

MIR580 (HGNC:32836): (microRNA 580) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMBRD2	NM_001007527.2	c.-58+3852G>A		intron_variant	Intron 1 of 17	ENST00000296603.5	NP_001007528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMBRD2	ENST00000296603.5	c.-58+3852G>A		intron_variant	Intron 1 of 17	1	NM_001007527.2	ENSP00000296603.4
MIR580	ENST00000385023.1	n.*188G>A		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47138 AN: 151888 Hom.: 8133 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.310 AC: 47138 AN: 152006 Hom.: 8126 Cov.: 32 AF XY: 0.309 AC XY: 22937 AN XY: 74278

African (AFR) AF: 0.171 AC: 7082 AN: 41468

American (AMR) AF: 0.343 AC: 5235 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1312 AN: 3468

East Asian (EAS) AF: 0.113 AC: 583 AN: 5180

South Asian (SAS) AF: 0.248 AC: 1196 AN: 4816

European-Finnish (FIN) AF: 0.411 AC: 4339 AN: 10548

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.386 AC: 26195 AN: 67936

Other (OTH) AF: 0.326 AC: 689 AN: 2112

Alfa AF: 0.339 Hom.: 4494

Bravo AF: 0.299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.62
PhyloP100		-0.014
Mutation Taster		=100/0	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: rs10071838; hg19: chr5-36147806;