20-63778360-C-T

Variant names:

• chr20-63778360-C-T
• rs6062314
• NM_001369741.1:c.938-2398G>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.938-2398G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 152,088 control chromosomes in the GnomAD database, including 60,711 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 0.89 (60711 hom., cov: 33)
• Consequence: ZBTB46 NM_001369741.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 42 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB46	NM_001369741.1	c.938-2398G>A		intron_variant	Intron 2 of 4	ENST00000245663.9	NP_001356670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB46	ENST00000245663.9	c.938-2398G>A		intron_variant	Intron 2 of 4	5	NM_001369741.1	ENSP00000245663.3
ZBTB46	ENST00000302995.2	c.938-2398G>A		intron_variant	Intron 2 of 6	2		ENSP00000303102.2
ZBTB46	ENST00000395104.5	c.938-2398G>A		intron_variant	Intron 1 of 3	2		ENSP00000378536.1
ZBTB46	ENST00000650966.1	n.938-2398G>A		intron_variant	Intron 2 of 5			ENSP00000498245.1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135435 AN: 151970 Hom.: 60692 Cov.: 33

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.939

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.920

Gnomad OTH AF: 0.918

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

GnomAD4 genome AF: 0.891 AC: 135502 AN: 152088 Hom.: 60711 Cov.: 33 AF XY: 0.894 AC XY: 66445 AN XY: 74360

African (AFR) AF: 0.792 AC: 32856 AN: 41476

American (AMR) AF: 0.939 AC: 14351 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 3326 AN: 3464

East Asian (EAS) AF: 0.987 AC: 5116 AN: 5182

South Asian (SAS) AF: 0.962 AC: 4642 AN: 4826

European-Finnish (FIN) AF: 0.908 AC: 9624 AN: 10600

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.920 AC: 62522 AN: 67948

Other (OTH) AF: 0.918 AC: 1936 AN: 2108

Alfa AF: 0.915 Hom.: 220847

Bravo AF: 0.892

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.60
PhyloP100		-1.2
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: rs6062314; hg19: chr20-62409713;