chr17-7462044-C-T

Variant names:

• chr17-7462044-C-T
• rs2070028218
• NM_001128833.2:c.2938G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001128833.2(ZBTB4):​c.2938G>A​(p.Ala980Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZBTB4 NM_001128833.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.730
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030776918).
• BP6: Variant 17-7462044-C-T is Benign according to our data. Variant chr17-7462044-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2237069.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2938G>A	p.Ala980Thr	missense	Exon 4 of 4	NP_001122305.1	Q9P1Z0
	ZBTB4	NM_020899.4		c.2938G>A	p.Ala980Thr	missense	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.2938G>A	p.Ala980Thr	missense	Exon 4 of 4	ENSP00000369973.4	Q9P1Z0
	ZBTB4	ENST00000311403.4	TSL:1	c.2938G>A	p.Ala980Thr	missense	Exon 4 of 4	ENSP00000307858.4	Q9P1Z0
	ZBTB4	ENST00000907857.1		c.2938G>A	p.Ala980Thr	missense	Exon 4 of 4	ENSP00000577916.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448674 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719678

African (AFR) AF: 0.00 AC: 0 AN: 33252

American (AMR) AF: 0.00 AC: 0 AN: 43414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24770

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 83968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1105218

Other (OTH) AF: 0.00 AC: 0 AN: 59808

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.3
DANN	Benign	0.79
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.024	N
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.73
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.051
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.096
MutPred		0.14		Gain of glycosylation at A980 (P = 4e-04)
MVP		0.043
MPC		0.42
ClinPred		0.035	T
GERP RS		2.9
Varity_R		0.016
gMVP		0.066

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: rs2070028218; hg19: chr17-7365363;