rs4942830

chr13-49445240-T-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETDB2	NM_001160308.3	c.-342+383T>A		intron_variant		ENST00000611815.2
SETDB2-PHF11	NR_135324.2	n.584+383T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETDB2	ENST00000611815.2	c.-342+383T>A		intron_variant		5	NM_001160308.3	P1
SETDB2	ENST00000354234.8	c.-342+383T>A		intron_variant		1
SETDB2	ENST00000481439.1	n.175-313T>A		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.555

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	4.8
Dann	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs4942830; hg19: chr13-50019376;