4-4320351-G-A

Variant names:

• chr4-4320351-G-A
• rs873924
• NM_145291.4:c.1622-289G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145291.4. 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
	ZBTB49	NM_145291.4	MANE Select	c.1622-289G>A		intron	N/A	NP_660334.3
	ZBTB49	NM_001330625.2		c.1622-289G>A		intron	N/A	NP_001317554.1
	ZBTB49	NR_138481.2		n.1622-289G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB49	ENST00000337872.9	TSL:1 MANE Select	c.1622-289G>A		intron	N/A	ENSP00000338807.4
	ZBTB49	ENST00000504302.1	TSL:1	c.464-289G>A		intron	N/A	ENSP00000421654.1
	ZBTB49	ENST00000503703.5	TSL:1	n.*818-289G>A		intron	N/A	ENSP00000424525.1

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

African (AFR) AF: 0.333 AC: 13807 AN: 41480

American (AMR) AF: 0.475 AC: 7259 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1267 AN: 3470

East Asian (EAS) AF: 0.476 AC: 2448 AN: 5138

South Asian (SAS) AF: 0.389 AC: 1877 AN: 4820

European-Finnish (FIN) AF: 0.438 AC: 4620 AN: 10552

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.453 AC: 30780 AN: 67948

Other (OTH) AF: 0.399 AC: 841 AN: 2110

Alfa AF: 0.425 Hom.: 1797

Bravo AF: 0.417

Asia WGS AF: 0.427 AC: 1486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	14
DANN	Benign	0.31
PhyloP100		0.041
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs873924; hg19: chr4-4322078;