rs71307668

chr13-49444704-CA-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001160308.3(SETDB2):c.-494del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (16037 hom., cov: 0)
  • Exomes 𝑓: 0.46 (119 hom.)
• Consequence: SETDB2 NM_001160308.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SETDB2	NM_001160308.3	c.-494del		5_prime_UTR_variant	1/14	ENST00000611815.2
SETDB2-PHF11	NR_135324.2	n.432del		non_coding_transcript_exon_variant	1/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SETDB2	ENST00000611815.2	c.-494del		5_prime_UTR_variant	1/14	5	NM_001160308.3	P1
SETDB2	ENST00000354234.8	c.-494del		5_prime_UTR_variant	1/15	1
SETDB2	ENST00000481439.1	n.22del		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65771 AN: 151644 Hom.: 16032 Cov.: 0

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.460 AC: 440 AN: 956 Hom.: 119 Cov.: 0 AF XY: 0.425 AC XY: 226 AN XY: 532

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.511

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.433 AC: 65781 AN: 151762 Hom.: 16037 Cov.: 0 AF XY: 0.433 AC XY: 32077 AN XY: 74160

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.470

Alfa AF: 0.246 Hom.: 707

Bravo AF: 0.424

Asia WGS AF: 0.421 AC: 1462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs71307668; hg19: chr13-50018840; COSMIC: COSV51643069; COSMIC: COSV51643069;