rs1322319

Positions:

• chr10-37856581-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000611278.4(ZNF248):​c.-271T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,142,014 control chromosomes in the GnomAD database, including 11,443 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 0.13 (1353 hom., cov: 32)
  • Exomes 𝑓: 0.14 (10090 hom.)
• Consequence: ZNF248 ENST00000611278.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF248	NM_021045.3	c.-125-49T>C		intron_variant		ENST00000395867.8	NP_066383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF248	ENST00000395867.8	c.-125-49T>C		intron_variant		1	NM_021045.3	ENSP00000379208	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19539 AN: 151950 Hom.: 1352 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.141 AC: 139190 AN: 989946 Hom.: 10090 Cov.: 29 AF XY: 0.141 AC XY: 65422 AN XY: 465050

Gnomad4 AFR exome AF: 0.0927

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.134

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.0656

Gnomad4 FIN exome AF: 0.0760

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.129 AC: 19544 AN: 152068 Hom.: 1353 Cov.: 32 AF XY: 0.128 AC XY: 9521 AN XY: 74318

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.0624

Gnomad4 FIN AF: 0.0916

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.143

Alfa AF: 0.132 Hom.: 158

Bravo AF: 0.139

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1322319; hg19: chr10-38145509;