rs1148274

Variant names:

• chr10-37818988-T-G
• rs1148274
• ENST00000485560.5:n.330+14037A>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701
• Publications: 6 publications found

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]

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000485560.5. 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
	ZNF248	NM_001267607.3		c.330+14037A>C		intron	N/A	NP_001254536.1
	ZNF248	NM_001352476.2		c.330+14037A>C		intron	N/A	NP_001339405.1
	ZNF248	NM_001352477.2		c.*51+12244A>C		intron	N/A	NP_001339406.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF248	ENST00000485560.5	TSL:1	n.330+14037A>C		intron	N/A	ENSP00000473904.1
	TLK2P2	ENST00000414066.1	TSL:6	n.1858A>C		non_coding_transcript_exon	Exon 2 of 2
	ZNF248	ENST00000615949.6	TSL:5	c.330+14037A>C		intron	N/A	ENSP00000477940.1

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9117 AN: 152102 Hom.: 350 Cov.: 32

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.: 12 AF XY: 0.0725 AC XY: 32340 AN XY: 445784

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: 0 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

GnomAD4 genome AF: 0.0599 AC: 9119 AN: 152220 Hom.: 351 Cov.: 32 AF XY: 0.0569 AC XY: 4238 AN XY: 74420

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: 0 AN: 5176

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4826

European-Finnish (FIN) AF: 0.0663 AC: 702 AN: 10596

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0896 AC: 6096 AN: 67998

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0794 Hom.: 260

Bravo AF: 0.0590

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.4
DANN	Benign	0.64
PhyloP100		0.70

Splicing

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

Other links and lift over

dbSNP: rs1148274; hg19: chr10-38107916;