rs1415701

Variant names:

• chr6-130024690-G-A
• rs1415701
• NM_032438.4:c.-16+2385G>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.-16+2385G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 151,980 control chromosomes in the GnomAD database, including 7,476 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 (7476 hom., cov: 32)
• Consequence: L3MBTL3 NM_032438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 42 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
L3MBTL3	NM_032438.4	c.-16+2385G>A		intron_variant	Intron 2 of 22	ENST00000361794.7	NP_115814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
L3MBTL3	ENST00000361794.7	c.-16+2385G>A		intron_variant	Intron 2 of 22	5	NM_032438.4	ENSP00000354526.2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46492 AN: 151862 Hom.: 7472 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.306 AC: 46529 AN: 151980 Hom.: 7476 Cov.: 32 AF XY: 0.306 AC XY: 22712 AN XY: 74290

African (AFR) AF: 0.386 AC: 15987 AN: 41466

American (AMR) AF: 0.335 AC: 5111 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 655 AN: 3466

East Asian (EAS) AF: 0.400 AC: 2059 AN: 5150

South Asian (SAS) AF: 0.281 AC: 1355 AN: 4826

European-Finnish (FIN) AF: 0.236 AC: 2495 AN: 10570

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17911 AN: 67916

Other (OTH) AF: 0.319 AC: 673 AN: 2108

Alfa AF: 0.285 Hom.: 18726

Bravo AF: 0.319

Asia WGS AF: 0.331 AC: 1151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-0.012
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: rs1415701; hg19: chr6-130345835;