rs224241

Variant names:

• chr16-3267036-A-G
• rs224241
• ENST00000703449.1:c.-171+3153A>G

Variant summary

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

The ENST00000703449.1(ZNF263):​c.-171+3153A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,168 control chromosomes in the GnomAD database, including 3,650 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 0.20 (3650 hom., cov: 32)
  • Exomes 𝑓: 0.38 (0 hom.)
• Consequence: ZNF263 ENST00000703449.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563
• Publications: 11 publications found

Genes affected

ZNF263 (HGNC:13056): (zinc finger protein 263) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and transcription cis-regulatory region binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LINC00921 (HGNC:26830): (long intergenic non-protein coding RNA 921)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000703449.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC00921	NR_033904.1		n.2002-90A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF263	ENST00000703449.1		c.-171+3153A>G		intron	N/A	ENSP00000515300.1	B4DI05
	LINC00921	ENST00000572123.4	TSL:5	n.188-90A>G		intron	N/A
	LINC00921	ENST00000573951.1	TSL:2	n.2027-90A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30160 AN: 152042 Hom.: 3651 Cov.: 32

Gnomad AFR AF: 0.0792

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.0387

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 2 AN: 6

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.198 AC: 30157 AN: 152160 Hom.: 3650 Cov.: 32 AF XY: 0.201 AC XY: 14945 AN XY: 74384

African (AFR) AF: 0.0790 AC: 3279 AN: 41524

American (AMR) AF: 0.292 AC: 4457 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3470

East Asian (EAS) AF: 0.0387 AC: 201 AN: 5188

South Asian (SAS) AF: 0.126 AC: 609 AN: 4828

European-Finnish (FIN) AF: 0.294 AC: 3109 AN: 10564

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17011 AN: 67998

Other (OTH) AF: 0.207 AC: 437 AN: 2110

Alfa AF: 0.234 Hom.: 595

Bravo AF: 0.196

Asia WGS AF: 0.0880 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.62
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs224241;

hg19: chr16-3317036;