rs873924

chr4-4320351-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_145291.4(ZBTB49):c.1622-289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,008 control chromosomes in the GnomAD database, including 13,402 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 0.42 (13402 hom., cov: 32)
• Consequence: ZBTB49 NM_145291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

Genes affected

ZBTB49 (HGNC:19883): (zinc finger and BTB domain containing 49) Enables DNA-binding transcription factor binding activity; sequence-specific DNA binding activity; and transcription coactivator binding activity. Involved in negative regulation of cell population proliferation; positive regulation of transcription by RNA polymerase II; and regulation of cell cycle. Located in cytosol; microtubule cytoskeleton; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB49	NM_145291.4	c.1622-289G>A		intron_variant		ENST00000337872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB49	ENST00000337872.9	c.1622-289G>A		intron_variant		1	NM_145291.4	P1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63452 AN: 151890 Hom.: 13387 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.418 AC: 63505 AN: 152008 Hom.: 13402 Cov.: 32 AF XY: 0.422 AC XY: 31316 AN XY: 74284

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.399

Alfa AF: 0.428 Hom.: 1741

Bravo AF: 0.417

Asia WGS AF: 0.427 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	14
Dann	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.35		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs873924; hg19: chr4-4322078;