Genetic Variant L3MBTL2:p.Ser683Ser (chr22-41230182-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_031488.5(L3MBTL2):c.2049G>A(p.Ser683Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 1,578,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00032 ( 0 hom. )

Consequence

L3MBTL2
NM_031488.5 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.44

Publications

0 publications found

Variant links:

Genes affected

L3MBTL2 (HGNC:18594): (L3MBTL histone methyl-lysine binding protein 2) Enables methylated histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to act upstream of or within several processes, including ectoderm development; regulation of histone modification; and stem cell proliferation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

L3MBTL2 links:

CHADL (HGNC:25165): (chondroadherin like) Enables collagen binding activity and collagen fibril binding activity. Involved in negative regulation of collagen fibril organization. Located in collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

CHADL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP6

Variant 22-41230182-G-A is Benign according to our data. Variant chr22-41230182-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2681366.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031488.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L3MBTL2	NM_031488.5	MANE Select	c.2049G>A	p.Ser683Ser	synonymous	Exon 17 of 17	NP_113676.2
	CHADL	NM_138481.2	MANE Select	c.2263-452C>T		intron	N/A	NP_612490.1	Q6NUI6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
L3MBTL2	ENST00000216237.10	TSL:1 MANE Select	c.2049G>A	p.Ser683Ser	synonymous	Exon 17 of 17	ENSP00000216237.5	Q969R5-1
CHADL	ENST00000216241.14	TSL:1 MANE Select	c.2263-452C>T		intron	N/A	ENSP00000216241.9	Q6NUI6-1
L3MBTL2	ENST00000466589.5	TSL:1	n.2583G>A		non_coding_transcript_exon	Exon 16 of 16

Frequencies

GnomAD3 genomes

AF:

0.000273

AC:

AN:

146652

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000750

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000694

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000538

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000143

AC:

AN:

251292

AF XY:

0.000118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000320

AC:

458

AN:

1431556

Hom.:

Cov.:

AF XY:

0.000320

AC XY:

228

AN XY:

711464

show subpopulations

African (AFR)

AF:

0.0000920

AC:

AN:

32600

American (AMR)

AF:

0.0000229

AC:

AN:

43658

Ashkenazi Jewish (ASJ)

AF:

0.0000399

AC:

AN:

25042

East Asian (EAS)

AF:

0.00

AC:

AN:

37418

South Asian (SAS)

AF:

0.0000233

AC:

AN:

86002

European-Finnish (FIN)

AF:

0.0000195

AC:

AN:

51236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.000401

AC:

438

AN:

1091748

Other (OTH)

AF:

0.000206

AC:

AN:

58262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000273

AC:

AN:

146652

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

AN XY:

71262

show subpopulations

African (AFR)

AF:

0.0000750

AC:

AN:

39990

American (AMR)

AF:

0.0000694

AC:

AN:

14404

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3426

East Asian (EAS)

AF:

0.00

AC:

AN:

4696

South Asian (SAS)

AF:

0.00

AC:

AN:

4390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.000538

AC:

AN:

66922

Other (OTH)

AF:

0.00

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.000283

Hom.:

Bravo

AF:

0.000257

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

EBV-positive nodal T- and NK-cell lymphoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.10

(source)

DANN

Benign

0.72

PhyloP100

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.40

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.40

Position offset: 2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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