chr18-48255611-G-T

Variant names:

• chr18-48255611-G-T
• rs1944584
• NM_001318841.2:c.-78-69616C>A

Variant summary

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

The ENST00000590800.6(ZBTB7C):​c.-78-69616C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0946 in 152,096 control chromosomes in the GnomAD database, including 1,101 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 0.095 (1101 hom., cov: 32)
• Consequence: ZBTB7C ENST00000590800.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590800.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB7C	NM_001318841.2	MANE Select	c.-78-69616C>A		intron	N/A	NP_001305770.1
	ZBTB7C	NM_001371284.1		c.-333-69616C>A		intron	N/A	NP_001358213.1
	ZBTB7C	NM_001371285.1		c.-255-69616C>A		intron	N/A	NP_001358214.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB7C	ENST00000590800.6	TSL:1 MANE Select	c.-78-69616C>A		intron	N/A	ENSP00000467877.1
	ZBTB7C	ENST00000585404.5	TSL:1	c.-307-69616C>A		intron	N/A	ENSP00000464724.1
	ZBTB7C	ENST00000586525.5	TSL:1	c.-205-69616C>A		intron	N/A	ENSP00000468537.1

Frequencies

GnomAD3 genomes AF: 0.0944 AC: 14351 AN: 151978 Hom.: 1097 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0592

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0910

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

GnomAD4 genome AF: 0.0946 AC: 14384 AN: 152096 Hom.: 1101 Cov.: 32 AF XY: 0.0992 AC XY: 7374 AN XY: 74352

African (AFR) AF: 0.197 AC: 8158 AN: 41418

American (AMR) AF: 0.0592 AC: 905 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3472

East Asian (EAS) AF: 0.186 AC: 962 AN: 5176

South Asian (SAS) AF: 0.120 AC: 579 AN: 4828

European-Finnish (FIN) AF: 0.107 AC: 1138 AN: 10586

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0302 AC: 2054 AN: 68014

Other (OTH) AF: 0.0919 AC: 194 AN: 2110

Alfa AF: 0.0228 Hom.: 12

Bravo AF: 0.0957

Asia WGS AF: 0.156 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.60
PhyloP100		0.36
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: rs1944584; hg19: chr18-45781982;