rs1148275

Variant names:

• chr10-37819551-A-G
• rs1148275
• ENST00000485560.5:n.330+13474T>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+13474T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0916 in 954,394 control chromosomes in the GnomAD database, including 5,061 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: 0.098 (4710 hom.)
• Consequence: ZNF248 ENST00000485560.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.96
• Publications: 2 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLK2P2		n.37819551A>G		intragenic_variant
ZNF248	NM_001267607.3	c.330+13474T>C		intron_variant	Intron 6 of 6		NP_001254536.1
ZNF248	NM_001352476.2	c.330+13474T>C		intron_variant	Intron 5 of 5		NP_001339405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF248	ENST00000485560.5	n.330+13474T>C		intron_variant	Intron 5 of 6	1		ENSP00000473904.1
TLK2P2	ENST00000414066.1	n.1295T>C		non_coding_transcript_exon_variant	Exon 2 of 2	6
ZNF248	ENST00000615949.6	c.330+13474T>C		intron_variant	Intron 6 of 6	5		ENSP00000477940.1

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9119 AN: 152138 Hom.: 350 Cov.: 32

Gnomad AFR AF: 0.0168

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00829

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.0709

GnomAD4 exome AF: 0.0976 AC: 78312 AN: 802138 Hom.: 4710 Cov.: 12 AF XY: 0.0927 AC XY: 39360 AN XY: 424796

African (AFR) AF: 0.0189 AC: 382 AN: 20214

American (AMR) AF: 0.0501 AC: 2187 AN: 43678

Ashkenazi Jewish (ASJ) AF: 0.0893 AC: 1968 AN: 22046

East Asian (EAS) AF: 0.00 AC: 0 AN: 36476

South Asian (SAS) AF: 0.0134 AC: 968 AN: 72392

European-Finnish (FIN) AF: 0.0712 AC: 3753 AN: 52686

Middle Eastern (MID) AF: 0.0991 AC: 285 AN: 2876

European-Non Finnish (NFE) AF: 0.127 AC: 65350 AN: 513514

Other (OTH) AF: 0.0894 AC: 3419 AN: 38256

GnomAD4 genome AF: 0.0599 AC: 9121 AN: 152256 Hom.: 351 Cov.: 32 AF XY: 0.0570 AC XY: 4240 AN XY: 74444

African (AFR) AF: 0.0168 AC: 699 AN: 41570

American (AMR) AF: 0.0643 AC: 984 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4824

European-Finnish (FIN) AF: 0.0662 AC: 701 AN: 10586

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

European-Non Finnish (NFE) AF: 0.0896 AC: 6095 AN: 68014

Other (OTH) AF: 0.0701 AC: 148 AN: 2110

Alfa AF: 0.0738 Hom.: 60

Bravo AF: 0.0590

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.4
DANN	Benign	0.57
PhyloP100		3.0

Splicing

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

Other links and lift over

dbSNP: rs1148275; hg19: chr10-38108479;