13-49488191-C-T

Variant names:

• chr13-49488191-C-T
• rs959421
• NM_001160308.3:c.1577-99C>T

Variant summary

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

The NM_001160308.3(SETDB2):​c.1577-99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,458,604 control chromosomes in the GnomAD database, including 385,978 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 0.78 (47627 hom., cov: 31)
  • Exomes 𝑓: 0.72 (338351 hom.)
• Consequence: SETDB2 NM_001160308.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 11 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETDB2	NM_001160308.3	MANE Select	c.1577-99C>T		intron	N/A	NP_001153780.1
	SETDB2-PHF11	NM_001320727.2		c.1576+2468C>T		intron	N/A	NP_001307656.1
	SETDB2	NM_031915.3		c.1613-99C>T		intron	N/A	NP_114121.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SETDB2	ENST00000611815.2	TSL:5 MANE Select	c.1577-99C>T		intron	N/A	ENSP00000482240.2
	SETDB2	ENST00000354234.8	TSL:1	c.1613-99C>T		intron	N/A	ENSP00000346175.5
	SETDB2	ENST00000317257.12	TSL:1	c.1577-99C>T		intron	N/A	ENSP00000326477.9

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119229 AN: 151986 Hom.: 47566 Cov.: 31

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.763

GnomAD4 exome AF: 0.717 AC: 937248 AN: 1306500 Hom.: 338351 Cov.: 21 AF XY: 0.718 AC XY: 458422 AN XY: 638656

African (AFR) AF: 0.935 AC: 27481 AN: 29402

American (AMR) AF: 0.785 AC: 17695 AN: 22536

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 13588 AN: 19200

East Asian (EAS) AF: 0.895 AC: 33784 AN: 37758

South Asian (SAS) AF: 0.718 AC: 44213 AN: 61620

European-Finnish (FIN) AF: 0.765 AC: 27261 AN: 35646

Middle Eastern (MID) AF: 0.731 AC: 2677 AN: 3662

European-Non Finnish (NFE) AF: 0.701 AC: 730945 AN: 1042678

Other (OTH) AF: 0.733 AC: 39604 AN: 53998

GnomAD4 genome AF: 0.785 AC: 119348 AN: 152104 Hom.: 47627 Cov.: 31 AF XY: 0.787 AC XY: 58506 AN XY: 74344

African (AFR) AF: 0.930 AC: 38625 AN: 41530

American (AMR) AF: 0.776 AC: 11863 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2416 AN: 3468

East Asian (EAS) AF: 0.869 AC: 4492 AN: 5168

South Asian (SAS) AF: 0.729 AC: 3510 AN: 4816

European-Finnish (FIN) AF: 0.767 AC: 8094 AN: 10558

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47852 AN: 67968

Other (OTH) AF: 0.759 AC: 1603 AN: 2112

Alfa AF: 0.745 Hom.: 4551

Bravo AF: 0.791

Asia WGS AF: 0.794 AC: 2759 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.7
DANN	Benign	0.66
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs959421; hg19: chr13-50062327;