chr11-114215695-G-A

Variant names:

• chr11-114215695-G-A
• rs495248
• NM_006006.6:c.1454-26472G>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.1454-26472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,152 control chromosomes in the GnomAD database, including 6,995 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 0.29 (6995 hom., cov: 33)
• Consequence: ZBTB16 NM_006006.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 0 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.363 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.1454-26472G>A		intron	N/A	NP_005997.2
	ZBTB16	NM_001018011.3		c.1454-26472G>A		intron	N/A	NP_001018011.1	A0A024R3C6
	ZBTB16	NM_001354750.2		c.1454-26472G>A		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.1454-26472G>A		intron	N/A	ENSP00000338157.4	Q05516-1
	ZBTB16	ENST00000392996.2	TSL:1	c.1454-26472G>A		intron	N/A	ENSP00000376721.2	Q05516-1
	ZBTB16	ENST00000865551.1		c.1454-26472G>A		intron	N/A	ENSP00000535610.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44693 AN: 152032 Hom.: 6983 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.294 AC: 44745 AN: 152152 Hom.: 6995 Cov.: 33 AF XY: 0.303 AC XY: 22553 AN XY: 74404

African (AFR) AF: 0.234 AC: 9703 AN: 41524

American (AMR) AF: 0.270 AC: 4123 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3468

East Asian (EAS) AF: 0.309 AC: 1596 AN: 5168

South Asian (SAS) AF: 0.378 AC: 1820 AN: 4818

European-Finnish (FIN) AF: 0.500 AC: 5287 AN: 10584

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20734 AN: 67990

Other (OTH) AF: 0.264 AC: 557 AN: 2108

Alfa AF: 0.292 Hom.: 25661

Bravo AF: 0.272

Asia WGS AF: 0.378 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.92
DANN	Benign	0.38
PhyloP100		-0.16
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: rs495248; hg19: chr11-114086417;