rs648044

Variant names:

• chr11-114160077-A-G
• rs648044
• NM_006006.6:c.1366+3643A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-114160077-A-G
• chr11-114160077-A-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006006.6(ZBTB16):​c.1366+3643A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,030 control chromosomes in the GnomAD database, including 34,498 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 0.66 (34498 hom., cov: 31)
• Consequence: ZBTB16 NM_006006.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.68
• Publications: 13 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)

ENSG00000286463 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB16	NM_006006.6	c.1366+3643A>G		intron_variant	Intron 3 of 6	ENST00000335953.9	NP_005997.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB16	ENST00000335953.9	c.1366+3643A>G		intron_variant	Intron 3 of 6	1	NM_006006.6	ENSP00000338157.4

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100803 AN: 151910 Hom.: 34453 Cov.: 31

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.664 AC: 100903 AN: 152030 Hom.: 34498 Cov.: 31 AF XY: 0.656 AC XY: 48753 AN XY: 74318

African (AFR) AF: 0.817 AC: 33870 AN: 41460

American (AMR) AF: 0.636 AC: 9730 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 2505 AN: 3468

East Asian (EAS) AF: 0.570 AC: 2924 AN: 5126

South Asian (SAS) AF: 0.536 AC: 2580 AN: 4816

European-Finnish (FIN) AF: 0.462 AC: 4886 AN: 10582

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42190 AN: 67972

Other (OTH) AF: 0.679 AC: 1435 AN: 2114

Alfa AF: 0.582 Hom.: 3760

Bravo AF: 0.681

Asia WGS AF: 0.572 AC: 1989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.24
DANN	Benign	0.75
PhyloP100		-4.7
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: rs648044; hg19: chr11-114030799;