rs2315656

Variant names:

• chr20-63786984-G-A
• rs2315656
• NM_001369741.1:c.937+2837C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.687 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB46	NM_001369741.1	MANE Select	c.937+2837C>T		intron	N/A	NP_001356670.1
	ZBTB46	NM_025224.4		c.937+2837C>T		intron	N/A	NP_079500.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB46	ENST00000245663.9	TSL:5 MANE Select	c.937+2837C>T		intron	N/A	ENSP00000245663.3
	ZBTB46	ENST00000302995.2	TSL:2	c.937+2837C>T		intron	N/A	ENSP00000303102.2
	ZBTB46	ENST00000395104.5	TSL:2	c.937+2837C>T		intron	N/A	ENSP00000378536.1

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

African (AFR) AF: 0.614 AC: 25461 AN: 41458

American (AMR) AF: 0.612 AC: 9337 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2239 AN: 3468

East Asian (EAS) AF: 0.697 AC: 3600 AN: 5166

South Asian (SAS) AF: 0.707 AC: 3401 AN: 4810

European-Finnish (FIN) AF: 0.619 AC: 6529 AN: 10540

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42794 AN: 67956

Other (OTH) AF: 0.636 AC: 1346 AN: 2116

Alfa AF: 0.628 Hom.: 104038

Bravo AF: 0.627

Asia WGS AF: 0.717 AC: 2495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.92
DANN	Benign	0.45
PhyloP100		-0.54
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: rs2315656; hg19: chr20-62418337;