dbSNP rs2071970: L3MBTL1:c.1285-530G>A (chr20-43532243-G-A) – 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.1285-530G>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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0640

Publications

2 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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 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.1285-530G>A	intron	N/A	NP_001364232.1	A0A3F2YNZ1
L3MBTL1	NM_032107.5		c.1219-530G>A	intron	N/A	NP_115479.4
L3MBTL1	NM_001377306.1		c.1285-530G>A	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.1285-530G>A	intron	N/A	ENSP00000398516.2	A0A3F2YNZ1
ENSG00000288000	ENST00000657241.1		c.1966-530G>A	intron	N/A	ENSP00000499734.1	A0A590UK80
L3MBTL1	ENST00000373135.8	TSL:1	c.1015-530G>A	intron	N/A	ENSP00000362227.3	Q9Y468-1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56185

AN:

151900

Hom.:

10980

Cov.:

show subpopulations

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:

AN:

214

Hom.:

Cov.:

AF XY:

0.330

AC XY:

AN XY:

100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.350

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.306

AC:

AN:

160

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.370

AC:

56275

AN:

152018

Hom.:

11018

Cov.:

AF XY:

0.365

AC XY:

27139

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.502

AC:

20806

AN:

41478

American (AMR)

AF:

0.358

AC:

5467

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1281

AN:

3472

East Asian (EAS)

AF:

0.453

AC:

2332

AN:

5150

South Asian (SAS)

AF:

0.357

AC:

1717

AN:

4812

European-Finnish (FIN)

AF:

0.257

AC:

2710

AN:

10564

Middle Eastern (MID)

AF:

0.387

AC:

113

AN:

292

European-Non Finnish (NFE)

AF:

0.305

AC:

20756

AN:

67974

Other (OTH)

AF:

0.378

AC:

796

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1799

3598

5396

7195

8994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.360

Hom.:

1895

Bravo

AF:

0.384

Asia WGS

AF:

0.433

AC:

1502

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.43

(source)

DANN

Benign

0.71

PhyloP100

-0.064

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over