rs2315656

Positions:

• chr20-63786984-G-A

Variant summary

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

The NM_001369741.1(ZBTB46):​c.937+2837C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,980 control chromosomes in the GnomAD database, including 29,947 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 0.63 (29947 hom., cov: 31)
• Consequence: ZBTB46 NM_001369741.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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]

ZBTB46 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB46	NM_001369741.1	c.937+2837C>T		intron_variant		ENST00000245663.9	NP_001356670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB46	ENST00000245663.9	c.937+2837C>T		intron_variant		5	NM_001369741.1	ENSP00000245663.3
ZBTB46	ENST00000302995.2	c.937+2837C>T		intron_variant		2		ENSP00000303102.2
ZBTB46	ENST00000395104.5	c.937+2837C>T		intron_variant		2		ENSP00000378536.1
ZBTB46	ENST00000650966.1	n.937+2837C>T		intron_variant				ENSP00000498245.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95376 AN: 151862 Hom.: 29916 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.628 AC: 95459 AN: 151980 Hom.: 29947 Cov.: 31 AF XY: 0.629 AC XY: 46697 AN XY: 74276

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.630

Gnomad4 OTH AF: 0.636

Alfa AF: 0.628 Hom.: 42435

Bravo AF: 0.627

Asia WGS AF: 0.717 AC: 2495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.92
DANN	Benign	0.45

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: rs2315656; hg19: chr20-62418337;