rs4942830

Variant names:

• chr13-49445240-T-A
• rs4942830
• NM_001160308.3:c.-342+383T>A

Variant summary

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

The NM_001160308.3(SETDB2):​c.-342+383T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,898 control chromosomes in the GnomAD database, including 23,376 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 0.55 (23376 hom., cov: 31)
• Consequence: SETDB2 NM_001160308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• Publications: 15 publications found

Genes affected

SETDB2 (HGNC:20263): (SET domain bifurcated histone lysine methyltransferase 2) This gene encodes a member of a family of proteins that contain a methyl-CpG-binding domain (MBD) and a SET domain and function as histone methyltransferases. This protein is recruited to heterochromatin and plays a role in the regulation of chromosome segregation. This region is commonly deleted in chronic lymphocytic leukemia. Naturally-occuring readthrough transcription occurs from this gene to the downstream PHF11 (PHD finger protein 11) gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

SETDB2-PHF11 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160308.3. 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
	SETDB2	NM_001160308.3	MANE Select	c.-342+383T>A		intron	N/A	NP_001153780.1	Q96T68-2
	SETDB2-PHF11	NM_001320727.2		c.-342+383T>A		intron	N/A	NP_001307656.1
	SETDB2	NM_031915.3		c.-342+383T>A		intron	N/A	NP_114121.2	Q96T68-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETDB2	ENST00000611815.2	TSL:5 MANE Select	c.-342+383T>A		intron	N/A	ENSP00000482240.2	Q96T68-2
	SETDB2	ENST00000354234.8	TSL:1	c.-342+383T>A		intron	N/A	ENSP00000346175.5	Q96T68-1
	SETDB2	ENST00000481439.1	TSL:1	n.175-313T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83936 AN: 151778 Hom.: 23353 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.553 AC: 83989 AN: 151898 Hom.: 23376 Cov.: 31 AF XY: 0.547 AC XY: 40608 AN XY: 74214

African (AFR) AF: 0.598 AC: 24777 AN: 41434

American (AMR) AF: 0.525 AC: 8017 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1809 AN: 3464

East Asian (EAS) AF: 0.508 AC: 2618 AN: 5152

South Asian (SAS) AF: 0.363 AC: 1748 AN: 4812

European-Finnish (FIN) AF: 0.537 AC: 5656 AN: 10542

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.554 AC: 37599 AN: 67916

Other (OTH) AF: 0.555 AC: 1171 AN: 2110

Alfa AF: 0.362 Hom.: 772

Bravo AF: 0.558

Asia WGS AF: 0.449 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.8
DANN	Benign	0.78
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4942830; hg19: chr13-50019376;