rs2239540

chr9-122912716-G-Achr9-122912716-G-Cchr9-122912716-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006626.6(ZBTB6):c.-10+535C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,926 control chromosomes in the GnomAD database, including 4,463 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 0.21 (4463 hom., cov: 32)
• Consequence: ZBTB6 NM_006626.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241

Genes affected

ZBTB6 (HGNC:16764): (zinc finger and BTB domain containing 6) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in mitochondrion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZBTB6	NM_006626.6	c.-10+535C>T		intron_variant		ENST00000373659.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZBTB6	ENST00000373659.4	c.-10+535C>T		intron_variant		1	NM_006626.6	P1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31090 AN: 151808 Hom.: 4437 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.205 AC: 31176 AN: 151926 Hom.: 4463 Cov.: 32 AF XY: 0.212 AC XY: 15707 AN XY: 74256

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.206

Alfa AF: 0.127 Hom.: 741

Bravo AF: 0.226

Asia WGS AF: 0.392 AC: 1358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.1
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2239540; hg19: chr9-125674995;