rs1944582

Variant names:

• chr18-48289046-A-G
• rs1944582
• NM_001318841.2:c.-79+49128T>C

Variant summary

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

The NM_001318841.2(ZBTB7C):​c.-79+49128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,976 control chromosomes in the GnomAD database, including 13,415 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 0.41 (13415 hom., cov: 32)
• Consequence: ZBTB7C NM_001318841.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 7 publications found

Genes affected

ZBTB7C (HGNC:31700): (zinc finger and BTB domain containing 7C) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of cell population proliferation. Predicted to be located in nucleus. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB7C	NM_001318841.2	c.-79+49128T>C		intron_variant	Intron 2 of 4	ENST00000590800.6	NP_001305770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB7C	ENST00000590800.6	c.-79+49128T>C		intron_variant	Intron 2 of 4	1	NM_001318841.2	ENSP00000467877.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62244 AN: 151858 Hom.: 13414 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.410 AC: 62242 AN: 151976 Hom.: 13415 Cov.: 32 AF XY: 0.404 AC XY: 29976 AN XY: 74290

African (AFR) AF: 0.302 AC: 12511 AN: 41448

American (AMR) AF: 0.323 AC: 4939 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1426 AN: 3466

East Asian (EAS) AF: 0.286 AC: 1480 AN: 5176

South Asian (SAS) AF: 0.455 AC: 2190 AN: 4816

European-Finnish (FIN) AF: 0.436 AC: 4593 AN: 10540

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33692 AN: 67942

Other (OTH) AF: 0.393 AC: 829 AN: 2112

Alfa AF: 0.454 Hom.: 47498

Bravo AF: 0.397

Asia WGS AF: 0.320 AC: 1113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.58
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1944582; hg19: chr18-45815417;