dbSNP rs71307668: SETDB2:c.-494delA (chr13-49444704-CA-C) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_001160308.3(SETDB2):c.-494delA 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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.68

Variant links:

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 links:

SETDB2-PHF11 (HGNC:):

SETDB2-PHF11 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
SETDB2	NM_001160308.3 link	c.-494delA		5_prime_UTR_variant	Exon 1 of 14	ENST00000611815.2	NP_001153780.1	Q96T68-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SETDB2	ENST00000611815 link	c.-494delA	5_prime_UTR_variant	Exon 1 of 14	5	NM_001160308.3	ENSP00000482240.2	Q96T68-2A0A087WYZ9
SETDB2	ENST00000354234 link	c.-494delA	5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000346175.5	Q96T68-1
SETDB2	ENST00000481439.1 link	n.22delA	non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65771

AN:

151644

Hom.:

16032

Cov.:

show subpopulations

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.:

AF XY:

0.425

AC XY:

226

AN XY:

532

show subpopulations

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.:

AF XY:

0.433

AC XY:

32077

AN XY:

74160

show subpopulations

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

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over