rs2844455

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_181842.3(ZBTB12):​c.-80G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 143,828 control chromosomes in the GnomAD database, including 10 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 0.0052 ( 10 hom., cov: 23)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ZBTB12
NM_181842.3 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.158
Variant links:
Genes affected
ZBTB12 (HGNC:19066): (zinc finger and BTB domain containing 12) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
C2 (HGNC:1248): (complement C2) Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BS2
High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZBTB12NM_181842.3 linkuse as main transcriptc.-80G>C 5_prime_UTR_variant 1/2 ENST00000375527.3 NP_862825.1 Q9Y330
C2NM_001178063.3 linkuse as main transcriptc.73+757C>G intron_variant NP_001171534.1 P06681-2
C2NM_001282457.2 linkuse as main transcriptc.-64+3954C>G intron_variant NP_001269386.1 B4DQI1Q53HP3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZBTB12ENST00000375527.3 linkuse as main transcriptc.-80G>C 5_prime_UTR_variant 1/21 NM_181842.3 ENSP00000364677.2 Q9Y330

Frequencies

GnomAD3 genomes
AF:
0.00517
AC:
743
AN:
143722
Hom.:
10
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.00679
Gnomad AMI
AF:
0.00242
Gnomad AMR
AF:
0.00234
Gnomad ASJ
AF:
0.000297
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000225
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00659
Gnomad OTH
AF:
0.00459
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
172
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
116
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00517
AC:
743
AN:
143828
Hom.:
10
Cov.:
23
AF XY:
0.00456
AC XY:
319
AN XY:
69894
show subpopulations
Gnomad4 AFR
AF:
0.00678
Gnomad4 AMR
AF:
0.00234
Gnomad4 ASJ
AF:
0.000297
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000225
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00659
Gnomad4 OTH
AF:
0.00454
Alfa
AF:
0.0000165
Hom.:
1112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
16
DANN
Benign
0.93
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
0.97

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2844455; hg19: chr6-31869673; API