dbSNP rs1148274: ZNF248:n.330+14037A>C (chr10-37818988-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000485560.5(ZNF248):n.330+14037A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 1,000,562 control chromosomes in the GnomAD database, including 3,205 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 0.060 ( 351 hom., cov: 32)

Exomes 𝑓: 0.074 ( 2854 hom. )

Consequence

ZNF248
ENST00000485560.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.701

Publications

6 publications found

Variant links:

Genes affected

ZNF248 (HGNC:13041): (zinc finger protein 248) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF248 links:

TLK2P2 (HGNC:22227): (tousled like kinase 2 pseudogene 2)

TLK2P2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
TLK2P2		n.37818988T>G	intragenic_variant
ZNF248	NM_001267607.3 link	c.330+14037A>C	intron_variant	Intron 6 of 6	NP_001254536.1	A0A087WTK3
ZNF248	NM_001352476.2 link	c.330+14037A>C	intron_variant	Intron 5 of 5	NP_001339405.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ZNF248	ENST00000485560.5 link	n.330+14037A>C	intron_variant	Intron 5 of 6	1	ENSP00000473904.1	S4R340
TLK2P2	ENST00000414066.1 link	n.1858A>C	non_coding_transcript_exon_variant	Exon 2 of 2	6
ZNF248	ENST00000615949.6 link	c.330+14037A>C	intron_variant	Intron 6 of 6	5	ENSP00000477940.1	A0A087WTK3

Frequencies

GnomAD3 genomes

AF:

0.0599

AC:

9117

AN:

152102

Hom.:

350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.0643

Gnomad ASJ

AF:

0.0845

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.0663

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0896

Gnomad OTH

AF:

0.0718

GnomAD4 exome

AF:

0.0743

AC:

63073

AN:

848342

Hom.:

2854

Cov.:

AF XY:

0.0725

AC XY:

32340

AN XY:

445784

show subpopulations

African (AFR)

AF:

0.0157

AC:

340

AN:

21598

American (AMR)

AF:

0.0496

AC:

2129

AN:

42926

Ashkenazi Jewish (ASJ)

AF:

0.0847

AC:

1807

AN:

21334

East Asian (EAS)

AF:

0.00

AC:

AN:

35926

South Asian (SAS)

AF:

0.0127

AC:

939

AN:

74034

European-Finnish (FIN)

AF:

0.0714

AC:

3608

AN:

50524

Middle Eastern (MID)

AF:

0.0877

AC:

247

AN:

2818

European-Non Finnish (NFE)

AF:

0.0912

AC:

51137

AN:

560546

Other (OTH)

AF:

0.0742

AC:

2866

AN:

38636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

3111

6222

9334

12445

15556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0599

AC:

9119

AN:

152220

Hom.:

351

Cov.:

AF XY:

0.0569

AC XY:

4238

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0168

AC:

698

AN:

41560

American (AMR)

AF:

0.0642

AC:

981

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0845

AC:

293

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00850

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0663

AC:

702

AN:

10596

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0896

AC:

6096

AN:

67998

Other (OTH)

AF:

0.0710

AC:

150

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

413

826

1239

1652

2065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0794

Hom.:

260

Bravo

AF:

0.0590

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

4.4

(source)

DANN

Benign

0.64

PhyloP100

0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs1148274

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over