rs549427

Variant names:

• chr11-114214137-G-A
• rs549427
• NM_006006.6:c.1453+27099G>A

Variant summary

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

The NM_006006.6(ZBTB16):​c.1453+27099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 152,154 control chromosomes in the GnomAD database, including 397 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 0.054 (397 hom., cov: 32)
• Consequence: ZBTB16 NM_006006.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 1 publications found

Genes affected

ZBTB16 (HGNC:12930): (zinc finger and BTB domain containing 16) This gene is a member of the Krueppel C2H2-type zinc-finger protein family and encodes a zinc finger transcription factor that contains nine Kruppel-type zinc finger domains at the carboxyl terminus. This protein is located in the nucleus, is involved in cell cycle progression, and interacts with a histone deacetylase. Specific instances of aberrant gene rearrangement at this locus have been associated with acute promyelocytic leukemia (APL). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

ZBTB16 Gene-Disease associations (from GenCC):

• skeletal defects, genital hypoplasia, and intellectual disability

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000256947 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.0714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB16	NM_006006.6	c.1453+27099G>A		intron_variant	Intron 4 of 6	ENST00000335953.9	NP_005997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB16	ENST00000335953.9	c.1453+27099G>A		intron_variant	Intron 4 of 6	1	NM_006006.6	ENSP00000338157.4

Frequencies

GnomAD3 genomes AF: 0.0543 AC: 8257 AN: 152036 Hom.: 397 Cov.: 32

Gnomad AFR AF: 0.0127

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0241

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0282

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.0468

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

GnomAD4 genome AF: 0.0543 AC: 8257 AN: 152154 Hom.: 397 Cov.: 32 AF XY: 0.0577 AC XY: 4289 AN XY: 74390

African (AFR) AF: 0.0126 AC: 523 AN: 41528

American (AMR) AF: 0.0240 AC: 367 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0305 AC: 106 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.0282 AC: 136 AN: 4822

European-Finnish (FIN) AF: 0.190 AC: 2015 AN: 10580

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0731 AC: 4968 AN: 67986

Other (OTH) AF: 0.0463 AC: 98 AN: 2116

Alfa AF: 0.0596 Hom.: 592

Bravo AF: 0.0412

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.76
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs549427; hg19: chr11-114084859;