rs4970986

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-150935479-A-G
• chr1-150935479-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• 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: Benign. The variant received -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.

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>G		intron	N/A	NP_001353347.1	A0A8I5KT93
	SETDB1	NM_001366417.1		c.413-4461A>G		intron	N/A	NP_001353346.1	A0A8I5KT93
	SETDB1	NM_001393958.1		c.413-4461A>G		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>G		intron	N/A	ENSP00000509425.1	A0A8I5KT93
	SETDB1	ENST00000271640.9	TSL:1	c.413-4461A>G		intron	N/A	ENSP00000271640.5	Q15047-1
	SETDB1	ENST00000368969.8	TSL:1	c.413-4461A>G		intron	N/A	ENSP00000357965.4	Q15047-3

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53513 AN: 150966 Hom.: 9814 Cov.: 30

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

African (AFR) AF: 0.281 AC: 11577 AN: 41128

American (AMR) AF: 0.472 AC: 7174 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1469 AN: 3462

East Asian (EAS) AF: 0.414 AC: 2134 AN: 5156

South Asian (SAS) AF: 0.511 AC: 2447 AN: 4790

European-Finnish (FIN) AF: 0.349 AC: 3581 AN: 10268

Middle Eastern (MID) AF: 0.390 AC: 113 AN: 290

European-Non Finnish (NFE) AF: 0.354 AC: 24034 AN: 67800

Other (OTH) AF: 0.365 AC: 764 AN: 2096

Alfa AF: 0.339 Hom.: 4566

Bravo AF: 0.358

Asia WGS AF: 0.427 AC: 1479 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.95
DANN	Benign	0.57
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4970986; hg19: chr1-150907955;