rs2073848

Variant names:

• chr11-114181182-T-C
• rs2073848
• NM_006006.6:c.1367-5770T>C

Variant summary

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

The NM_006006.6(ZBTB16):​c.1367-5770T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,278 control chromosomes in the GnomAD database, including 1,490 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 0.13 (1490 hom., cov: 33)
• Consequence: ZBTB16 NM_006006.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 5 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006006.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB16	NM_006006.6	MANE Select	c.1367-5770T>C		intron	N/A	NP_005997.2
	ZBTB16	NM_001018011.3		c.1367-5770T>C		intron	N/A	NP_001018011.1	A0A024R3C6
	ZBTB16	NM_001354750.2		c.1367-5770T>C		intron	N/A	NP_001341679.1	Q05516-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB16	ENST00000335953.9	TSL:1 MANE Select	c.1367-5770T>C		intron	N/A	ENSP00000338157.4	Q05516-1
	ZBTB16	ENST00000392996.2	TSL:1	c.1367-5770T>C		intron	N/A	ENSP00000376721.2	Q05516-1
	ZBTB16	ENST00000541602.5	TSL:1	n.1615-5770T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19028 AN: 152160 Hom.: 1485 Cov.: 33

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.125 AC: 19036 AN: 152278 Hom.: 1490 Cov.: 33 AF XY: 0.126 AC XY: 9374 AN XY: 74452

African (AFR) AF: 0.0389 AC: 1616 AN: 41556

American (AMR) AF: 0.103 AC: 1576 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 536 AN: 3472

East Asian (EAS) AF: 0.227 AC: 1179 AN: 5188

South Asian (SAS) AF: 0.188 AC: 906 AN: 4826

European-Finnish (FIN) AF: 0.147 AC: 1560 AN: 10602

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11238 AN: 68008

Other (OTH) AF: 0.110 AC: 233 AN: 2112

Alfa AF: 0.149 Hom.: 3184

Bravo AF: 0.116

Asia WGS AF: 0.212 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		-0.063
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: rs2073848; hg19: chr11-114051904;