chr4-4290788-T-C

Position:

• chr4-4290788-T-C

Variant summary

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

The NM_145291.4(ZBTB49):​c.-20+436T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,120 control chromosomes in the GnomAD database, including 11,124 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 0.37 (11124 hom., cov: 34)
• Consequence: ZBTB49 NM_145291.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB49	NM_145291.4	c.-20+436T>C		intron_variant		ENST00000337872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB49	ENST00000337872.9	c.-20+436T>C		intron_variant		1	NM_145291.4	P1
ZBTB49	ENST00000503703.5	c.-20+436T>C		intron_variant, NMD_transcript_variant		1
ZBTB49	ENST00000515012.5	c.-20+436T>C		intron_variant, NMD_transcript_variant		1
ZBTB49	ENST00000502918.1	c.-20+475T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56890 AN: 152002 Hom.: 11110 Cov.: 34

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.374 AC: 56932 AN: 152120 Hom.: 11124 Cov.: 34 AF XY: 0.381 AC XY: 28293 AN XY: 74354

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.326

Alfa AF: 0.356 Hom.: 1212

Bravo AF: 0.373

Asia WGS AF: 0.439 AC: 1529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.74
DANN	Benign	0.61

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: rs920683; hg19: chr4-4292515;