chr1-150935479-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001366418.1(SETDB1):​c.413-4461A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 151,082 control chromosomes in the GnomAD database, including 9,825 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 0.35 ( 9825 hom., cov: 30)

Consequence

SETDB1
NM_001366418.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.262
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SETDB1NM_001366418.1 linkuse as main transcriptc.413-4461A>G intron_variant ENST00000692827.1 NP_001353347.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SETDB1ENST00000692827.1 linkuse as main transcriptc.413-4461A>G intron_variant NM_001366418.1 ENSP00000509425 A1

Frequencies

GnomAD3 genomes
AF:
0.354
AC:
53513
AN:
150966
Hom.:
9814
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.282
Gnomad AMI
AF:
0.264
Gnomad AMR
AF:
0.472
Gnomad ASJ
AF:
0.424
Gnomad EAS
AF:
0.414
Gnomad SAS
AF:
0.512
Gnomad FIN
AF:
0.349
Gnomad MID
AF:
0.401
Gnomad NFE
AF:
0.354
Gnomad OTH
AF:
0.361
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.354
AC:
53533
AN:
151082
Hom.:
9825
Cov.:
30
AF XY:
0.360
AC XY:
26578
AN XY:
73786
show subpopulations
Gnomad4 AFR
AF:
0.281
Gnomad4 AMR
AF:
0.472
Gnomad4 ASJ
AF:
0.424
Gnomad4 EAS
AF:
0.414
Gnomad4 SAS
AF:
0.511
Gnomad4 FIN
AF:
0.349
Gnomad4 NFE
AF:
0.354
Gnomad4 OTH
AF:
0.365
Alfa
AF:
0.337
Hom.:
4061
Bravo
AF:
0.358
Asia WGS
AF:
0.427
AC:
1479
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.95
DANN
Benign
0.57

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4970986; hg19: chr1-150907955; API