rs2275294

Positions:

• chr20-63962894-G-A
• chr20-63962894-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020713.3(ZNF512B):​c.1969-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,295,078 control chromosomes in the GnomAD database, including 48,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5614 hom., cov: 34)
  • Exomes 𝑓: 0.26 (43352 hom.)
• Consequence: ZNF512B NM_020713.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.200

Genes affected

ZNF512B (HGNC:29212): (zinc finger protein 512B) Predicted to enable DNA binding activity and metal ion binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-63962894-G-A is Benign according to our data. Variant chr20-63962894-G-A is described in ClinVar as [Benign]. Clinvar id is 1234322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF512B	NM_020713.3	c.1969-113C>T		intron_variant		ENST00000369888.6	NP_065764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF512B	ENST00000369888.6	c.1969-113C>T		intron_variant		1	NM_020713.3	ENSP00000358904.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38538 AN: 152032 Hom.: 5609 Cov.: 34

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.265 AC: 302780 AN: 1142928 Hom.: 43352 AF XY: 0.266 AC XY: 148791 AN XY: 559624

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.393

Gnomad4 EAS exome AF: 0.533

Gnomad4 SAS exome AF: 0.304

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.248

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.253 AC: 38557 AN: 152150 Hom.: 5614 Cov.: 34 AF XY: 0.257 AC XY: 19117 AN XY: 74372

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.281

Alfa AF: 0.256 Hom.: 1579

Bravo AF: 0.259

Asia WGS AF: 0.394 AC: 1367 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	This variant is associated with the following publications: (PMID: 21665992) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2275294; hg19: chr20-62594247; COSMIC: COSV53872143;