Genetic Variant NM_001366418.1:c.413-9C>T (chr1-150939931-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001366418.1(SETDB1):c.413-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000767 in 1,609,220 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 (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00079 ( 0 hom. )

Consequence

SETDB1
NM_001366418.1 intron

Scores

Splicing: ADA: 0.02936

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0830

Publications

1 publications found

Variant links:

Genes affected

SETDB1 (HGNC:10761): (SET domain bifurcated histone lysine methyltransferase 1) This gene encodes a histone methyltransferase which regulates histone methylation, gene silencing, and transcriptional repression. This gene has been identified as a target for treatment in Huntington Disease, given that gene silencing and transcription dysfunction likely play a role in the disease pathogenesis. Alternatively spliced transcript variants of this gene have been described.[provided by RefSeq, Jun 2011]

SETDB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 1-150939931-C-T is Benign according to our data. Variant chr1-150939931-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 723281.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 79 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366418.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SETDB1	NM_001366418.1	MANE Select	c.413-9C>T	intron	N/A	NP_001353347.1	A0A8I5KT93
SETDB1	NM_001366417.1		c.413-9C>T	intron	N/A	NP_001353346.1	A0A8I5KT93
SETDB1	NM_001393958.1		c.413-9C>T	intron	N/A	NP_001380887.1	A0A8I5KT93

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SETDB1	ENST00000692827.1	MANE Select	c.413-9C>T	intron	N/A	ENSP00000509425.1	A0A8I5KT93
SETDB1	ENST00000271640.9	TSL:1	c.413-9C>T	intron	N/A	ENSP00000271640.5	Q15047-1
SETDB1	ENST00000368969.8	TSL:1	c.413-9C>T	intron	N/A	ENSP00000357965.4	Q15047-3

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000983

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000396

AC:

AN:

249768

AF XY:

0.000385

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000743

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000793

AC:

1155

AN:

1456970

Hom.:

Cov.:

AF XY:

0.000756

AC XY:

548

AN XY:

725014

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33344

American (AMR)

AF:

0.000294

AC:

AN:

44252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25994

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.0000350

AC:

AN:

85816

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.000695

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000975

AC:

1081

AN:

1108628

Other (OTH)

AF:

0.000798

AC:

AN:

60174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

146

194

243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

132

176

220

<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:

0.000519

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41546

American (AMR)

AF:

0.000982

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68018

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.000549

Hom.:

Bravo

AF:

0.000646

EpiCase

AF:

0.000767

EpiControl

AF:

0.000890

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.083

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.029

dbscSNV1_RF

Benign

0.36

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

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