dbSNP rs2285185: L3MBTL1:c.1285-685C>T (chr20-43532088-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Publications

1 publications found

Variant links:

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]

L3MBTL1 links:

ENSG00000288000 (HGNC:):

ENSG00000288000 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377303.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
L3MBTL1	NM_001377303.1	MANE Select	c.1285-685C>T	intron	N/A	NP_001364232.1	A0A3F2YNZ1
L3MBTL1	NM_032107.5		c.1219-685C>T	intron	N/A	NP_115479.4
L3MBTL1	NM_001377306.1		c.1285-685C>T	intron	N/A	NP_001364235.1	A0A3B3ISS0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
L3MBTL1	ENST00000418998.7	TSL:2 MANE Select	c.1285-685C>T	intron	N/A	ENSP00000398516.2	A0A3F2YNZ1
ENSG00000288000	ENST00000657241.1		c.1966-685C>T	intron	N/A	ENSP00000499734.1	A0A590UK80
L3MBTL1	ENST00000373135.8	TSL:1	c.1015-685C>T	intron	N/A	ENSP00000362227.3	Q9Y468-1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31339

AN:

151930

Hom.:

3543

Cov.:

show subpopulations

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:

AN:

164

Hom.:

Cov.:

AF XY:

0.211

AC XY:

AN XY:

128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.232

AC:

AN:

138

Other (OTH)

AF:

0.100

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.206

AC:

31383

AN:

152048

Hom.:

3551

Cov.:

AF XY:

0.201

AC XY:

14947

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.289

AC:

11964

AN:

41448

American (AMR)

AF:

0.166

AC:

2540

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

918

AN:

3468

East Asian (EAS)

AF:

0.0908

AC:

469

AN:

5164

South Asian (SAS)

AF:

0.195

AC:

940

AN:

4816

European-Finnish (FIN)

AF:

0.151

AC:

1599

AN:

10578

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12251

AN:

67972

Other (OTH)

AF:

0.228

AC:

482

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1235

2469

3704

4938

6173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.192

Hom.:

384

Bravo

AF:

0.210

Asia WGS

AF:

0.169

AC:

586

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.3

(source)

DANN

Benign

0.90

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over