1-150935479-A-T

Variant names:

• chr1-150935479-A-T
• rs4970986
• NM_001366418.1:c.413-4461A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001366418.1(SETDB1):​c.413-4461A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: SETDB1 NM_001366418.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 16 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETDB1	NM_001366418.1	MANE Select	c.413-4461A>T		intron	N/A	NP_001353347.1	A0A8I5KT93
	SETDB1	NM_001366417.1		c.413-4461A>T		intron	N/A	NP_001353346.1	A0A8I5KT93
	SETDB1	NM_001393958.1		c.413-4461A>T		intron	N/A	NP_001380887.1	A0A8I5KT93

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETDB1	ENST00000692827.1	MANE Select	c.413-4461A>T		intron	N/A	ENSP00000509425.1	A0A8I5KT93
	SETDB1	ENST00000271640.9	TSL:1	c.413-4461A>T		intron	N/A	ENSP00000271640.5	Q15047-1
	SETDB1	ENST00000368969.8	TSL:1	c.413-4461A>T		intron	N/A	ENSP00000357965.4	Q15047-3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151068 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151068 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 73714

African (AFR) AF: 0.00 AC: 0 AN: 41034

American (AMR) AF: 0.00 AC: 0 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67838

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 4566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.70
DANN	Benign	0.47
PhyloP100		-0.26

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4970986;

hg19: chr1-150907955;