rs2285185

Positions:

• chr20-43532088-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377303.1(L3MBTL1):​c.1285-685C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,212 control chromosomes in the GnomAD database, including 3,554 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 0.21 (3551 hom., cov: 32)
  • Exomes 𝑓: 0.20 (3 hom.)
• Consequence: L3MBTL1 NM_001377303.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

L3MBTL1 (HGNC:15905): (L3MBTL histone methyl-lysine binding protein 1) This gene represents a polycomb group gene. The encoded protein functions to regulate gene activity, likely via chromatin modification. The encoded protein may also be necessary for mitosis. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
L3MBTL1	NM_001377303.1	c.1285-685C>T		intron_variant		ENST00000418998.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
L3MBTL1	ENST00000418998.7	c.1285-685C>T		intron_variant		2	NM_001377303.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31339 AN: 151930 Hom.: 3543 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0906

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.201 AC: 33 AN: 164 Hom.: 3 Cov.: 0 AF XY: 0.211 AC XY: 27 AN XY: 128

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.206 AC: 31383 AN: 152048 Hom.: 3551 Cov.: 32 AF XY: 0.201 AC XY: 14947 AN XY: 74310

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.0908

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.228

Alfa AF: 0.189 Hom.: 359

Bravo AF: 0.210

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.90

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: rs2285185; hg19: chr20-42160728;