6-130112145-G-A

Variant names:

• chr6-130112145-G-A
• rs9321208
• NM_032438.4:c.1886+7570G>A

Variant summary

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

The NM_032438.4(L3MBTL3):​c.1886+7570G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,102 control chromosomes in the GnomAD database, including 5,115 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 0.23 (5115 hom., cov: 32)
• Consequence: L3MBTL3 NM_032438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670
• Publications: 7 publications found

Genes affected

L3MBTL3 (HGNC:23035): (L3MBTL histone methyl-lysine binding protein 3) This gene encodes a member of the malignant brain tumor (MBT) family of chromatin interacting transcriptional repressors. Members of this family function as methyl-lysine readers, which recognize methylated lysine residues on histone protein tails, and are associated with the repression of gene expression. The encoded protein may regulate hematopoiesis. Homozygous deletion of this gene has been observed in human patients with medulloblastoma. [provided by RefSeq, Oct 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L3MBTL3	NM_032438.4	c.1886+7570G>A		intron_variant	Intron 19 of 22	ENST00000361794.7	NP_115814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L3MBTL3	ENST00000361794.7	c.1886+7570G>A		intron_variant	Intron 19 of 22	5	NM_032438.4	ENSP00000354526.2

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34810 AN: 151984 Hom.: 5116 Cov.: 32

Gnomad AFR AF: 0.0768

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0370

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.229 AC: 34807 AN: 152102 Hom.: 5115 Cov.: 32 AF XY: 0.225 AC XY: 16714 AN XY: 74376

African (AFR) AF: 0.0767 AC: 3186 AN: 41516

American (AMR) AF: 0.185 AC: 2820 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3468

East Asian (EAS) AF: 0.0365 AC: 189 AN: 5182

South Asian (SAS) AF: 0.139 AC: 667 AN: 4810

European-Finnish (FIN) AF: 0.330 AC: 3485 AN: 10560

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22681 AN: 67964

Other (OTH) AF: 0.225 AC: 476 AN: 2116

Alfa AF: 0.297 Hom.: 14389

Bravo AF: 0.213

Asia WGS AF: 0.0850 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.75
PhyloP100		0.067
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: rs9321208; hg19: chr6-130433290;