chr17-7459769-T-C

Variant names:

• chr17-7459769-T-C
• rs9217
• NM_001128833.2:c.*2171A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128833.2(ZBTB4):​c.*2171A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,310 control chromosomes in the GnomAD database, including 10,032 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.36 (9999 hom., cov: 31)
  • Exomes 𝑓: 0.41 (33 hom.)
• Consequence: ZBTB4 NM_001128833.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• Publications: 48 publications found

Genes affected

ZBTB4 (HGNC:23847): (zinc finger and BTB domain containing 4) Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; methyl-CpNpG binding activity; and sequence-specific DNA binding activity. Involved in cellular response to DNA damage stimulus and negative regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128833.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB4	NM_001128833.2	MANE Select	c.*2171A>G		3_prime_UTR	Exon 4 of 4	NP_001122305.1	Q9P1Z0
	ZBTB4	NM_020899.4		c.*2171A>G		3_prime_UTR	Exon 4 of 4	NP_065950.2	Q9P1Z0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB4	ENST00000380599.9	TSL:1 MANE Select	c.*2171A>G		3_prime_UTR	Exon 4 of 4	ENSP00000369973.4	Q9P1Z0
	ZBTB4	ENST00000311403.4	TSL:1	c.*2171A>G		3_prime_UTR	Exon 4 of 4	ENSP00000307858.4	Q9P1Z0
	ZBTB4	ENST00000907857.1		c.*2171A>G		3_prime_UTR	Exon 4 of 4	ENSP00000577916.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54576 AN: 151764 Hom.: 9988 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.365

GnomAD4 exome AF: 0.414 AC: 178 AN: 430 Hom.: 33 Cov.: 0 AF XY: 0.404 AC XY: 101 AN XY: 250

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.413 AC: 175 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.360 AC: 54610 AN: 151880 Hom.: 9999 Cov.: 31 AF XY: 0.363 AC XY: 26965 AN XY: 74204

African (AFR) AF: 0.353 AC: 14619 AN: 41394

American (AMR) AF: 0.352 AC: 5360 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1112 AN: 3472

East Asian (EAS) AF: 0.234 AC: 1213 AN: 5182

South Asian (SAS) AF: 0.493 AC: 2374 AN: 4816

European-Finnish (FIN) AF: 0.415 AC: 4357 AN: 10492

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.358 AC: 24299 AN: 67964

Other (OTH) AF: 0.370 AC: 782 AN: 2114

Alfa AF: 0.352 Hom.: 37950

Bravo AF: 0.353

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.57
PhyloP100		0.46
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: rs9217; hg19: chr17-7363088;