rs765147

Positions:

• chr20-43493812-C-T

Variant summary

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

The ENST00000649501.1(L3MBTL1):​c.-101+4365C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,654 control chromosomes in the GnomAD database, including 20,936 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 0.52 (20936 hom., cov: 32)
• Consequence: L3MBTL1 ENST00000649501.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
L3MBTL1	ENST00000649501.1	c.-101+4365C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.521 AC: 78877 AN: 151536 Hom.: 20901 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.521 AC: 78966 AN: 151654 Hom.: 20936 Cov.: 32 AF XY: 0.524 AC XY: 38808 AN XY: 74116

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.648

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.514

Alfa AF: 0.463 Hom.: 27227

Bravo AF: 0.535

Asia WGS AF: 0.607 AC: 2108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs765147; hg19: chr20-42122452;