rs6089982

Variant names:

• chr20-63769790-C-T
• rs6089982
• NM_001369741.1:c.1222+5888G>A

Variant summary

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

The NM_001369741.1(ZBTB46):​c.1222+5888G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,226 control chromosomes in the GnomAD database, including 1,760 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 (1760 hom., cov: 33)
• Consequence: ZBTB46 NM_001369741.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 14 publications found

Genes affected

ZBTB46 (HGNC:16094): (zinc finger and BTB domain containing 46) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of leukocyte differentiation. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369741.1. 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
	ZBTB46	NM_001369741.1	MANE Select	c.1222+5888G>A		intron	N/A	NP_001356670.1	Q86UZ6
	ZBTB46	NM_025224.4		c.1222+5888G>A		intron	N/A	NP_079500.2	Q86UZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB46	ENST00000245663.9	TSL:5 MANE Select	c.1222+5888G>A		intron	N/A	ENSP00000245663.3	Q86UZ6
	ZBTB46	ENST00000395104.5	TSL:2	c.1222+5888G>A		intron	N/A	ENSP00000378536.1	Q86UZ6
	ZBTB46	ENST00000906793.1		c.1222+5888G>A		intron	N/A	ENSP00000576852.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19591 AN: 152110 Hom.: 1761 Cov.: 33

Gnomad AFR AF: 0.0454

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.129 AC: 19594 AN: 152226 Hom.: 1760 Cov.: 33 AF XY: 0.132 AC XY: 9799 AN XY: 74418

African (AFR) AF: 0.0454 AC: 1885 AN: 41546

American (AMR) AF: 0.170 AC: 2601 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3466

East Asian (EAS) AF: 0.473 AC: 2442 AN: 5164

South Asian (SAS) AF: 0.195 AC: 940 AN: 4824

European-Finnish (FIN) AF: 0.110 AC: 1171 AN: 10600

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9678 AN: 68024

Other (OTH) AF: 0.128 AC: 271 AN: 2112

Alfa AF: 0.142 Hom.: 2126

Bravo AF: 0.128

Asia WGS AF: 0.322 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.65
PhyloP100		0.023
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6089982; hg19: chr20-62401143;