rs1944574

Variant names:

• chr18-48198892-G-T
• rs1944574
• NM_001318841.2:c.-78-12897C>A

Variant summary

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

The NM_001318841.2(ZBTB7C):​c.-78-12897C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,214 control chromosomes in the GnomAD database, including 1,515 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 0.12 (1515 hom., cov: 32)
• Consequence: ZBTB7C NM_001318841.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366
• Publications: 1 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 = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB7C	NM_001318841.2	c.-78-12897C>A		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.-78-12897C>A		intron_variant	Intron 2 of 4	1	NM_001318841.2	ENSP00000467877.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18447 AN: 152096 Hom.: 1514 Cov.: 32

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.0866

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.121 AC: 18442 AN: 152214 Hom.: 1515 Cov.: 32 AF XY: 0.120 AC XY: 8951 AN XY: 74406

African (AFR) AF: 0.0314 AC: 1306 AN: 41538

American (AMR) AF: 0.0848 AC: 1297 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0866 AC: 300 AN: 3466

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.112 AC: 540 AN: 4824

European-Finnish (FIN) AF: 0.200 AC: 2115 AN: 10592

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12471 AN: 68002

Other (OTH) AF: 0.109 AC: 231 AN: 2112

Alfa AF: 0.162 Hom.: 431

Bravo AF: 0.108

Asia WGS AF: 0.0450 AC: 157 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	7.9
DANN	Benign	0.76
PhyloP100		0.37
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: rs1944574; hg19: chr18-45725263;