rs2071970

Positions:

• chr20-43532243-G-A

Variant summary

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

The NM_001377303.1(L3MBTL1):​c.1285-530G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,232 control chromosomes in the GnomAD database, including 11,030 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 0.37 (11018 hom., cov: 32)
  • Exomes 𝑓: 0.31 (12 hom.)
• Consequence: L3MBTL1 NM_001377303.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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]

ENSG00000288000 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
L3MBTL1	NM_001377303.1	c.1285-530G>A		intron_variant		ENST00000418998.7	NP_001364232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
L3MBTL1	ENST00000418998.7	c.1285-530G>A		intron_variant		2	NM_001377303.1	ENSP00000398516.2
ENSG00000288000	ENST00000657241.1	c.1966-530G>A		intron_variant				ENSP00000499734.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56185 AN: 151900 Hom.: 10980 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.308 AC: 66 AN: 214 Hom.: 12 Cov.: 0 AF XY: 0.330 AC XY: 33 AN XY: 100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.370 AC: 56275 AN: 152018 Hom.: 11018 Cov.: 32 AF XY: 0.365 AC XY: 27139 AN XY: 74298

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.378

Alfa AF: 0.357 Hom.: 1817

Bravo AF: 0.384

Asia WGS AF: 0.433 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.43
DANN	Benign	0.71

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: rs2071970; hg19: chr20-42160883;