18-48339226-A-G

Variant names:

• chr18-48339226-A-G
• rs11082671
• NM_001318841.2:c.-303-828T>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.-303-828T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,134 control chromosomes in the GnomAD database, including 24,761 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 0.57 (24761 hom., cov: 33)
• Consequence: ZBTB7C NM_001318841.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB7C	NM_001318841.2	c.-303-828T>C		intron_variant	Intron 1 of 4	ENST00000590800.6	NP_001305770.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB7C	ENST00000590800.6	c.-303-828T>C		intron_variant	Intron 1 of 4	1	NM_001318841.2	ENSP00000467877.1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86184 AN: 152016 Hom.: 24727 Cov.: 33

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.567 AC: 86280 AN: 152134 Hom.: 24761 Cov.: 33 AF XY: 0.576 AC XY: 42829 AN XY: 74388

African (AFR) AF: 0.531 AC: 22035 AN: 41502

American (AMR) AF: 0.607 AC: 9292 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 2001 AN: 3472

East Asian (EAS) AF: 0.791 AC: 4072 AN: 5148

South Asian (SAS) AF: 0.637 AC: 3067 AN: 4816

European-Finnish (FIN) AF: 0.640 AC: 6790 AN: 10604

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37017 AN: 67978

Other (OTH) AF: 0.578 AC: 1221 AN: 2114

Alfa AF: 0.552 Hom.: 8450

Bravo AF: 0.566

Asia WGS AF: 0.679 AC: 2356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.047
DANN	Benign	0.43
PhyloP100		-1.5
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: rs11082671; hg19: chr18-45865597;