rs764255

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001386735.1(ZFHX3):​c.-1064+396G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,010 control chromosomes in the GnomAD database, including 25,797 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 0.57 ( 25797 hom., cov: 32)
Exomes 𝑓: 0.33 ( 0 hom. )

Consequence

ZFHX3
NM_001386735.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.316
Variant links:
Genes affected
ZFHX3 (HGNC:777): (zinc finger homeobox 3) This gene encodes a transcription factor with multiple homeodomains and zinc finger motifs, and regulates myogenic and neuronal differentiation. The encoded protein suppresses expression of the alpha-fetoprotein gene by binding to an AT-rich enhancer motif. The protein has also been shown to negatively regulate c-Myb, and transactivate the cell cycle inhibitor cyclin-dependent kinase inhibitor 1A (also known as p21CIP1). This gene is reported to function as a tumor suppressor in several cancers, and sequence variants of this gene are also associated with atrial fibrillation. Multiple transcript variants expressed from alternate promoters and encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZFHX3NM_001386735.1 linkuse as main transcriptc.-1064+396G>A intron_variant NP_001373664.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZFHX3ENST00000641206.2 linkuse as main transcriptc.-1547+396G>A intron_variant ENSP00000493252 P1Q15911-1
ZFHX3ENST00000641018.1 linkuse as main transcriptn.557G>A non_coding_transcript_exon_variant 2/2
ZFHX3ENST00000642085.1 linkuse as main transcriptn.163+396G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.568
AC:
86243
AN:
151886
Hom.:
25798
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.361
Gnomad AMI
AF:
0.649
Gnomad AMR
AF:
0.652
Gnomad ASJ
AF:
0.784
Gnomad EAS
AF:
0.788
Gnomad SAS
AF:
0.674
Gnomad FIN
AF:
0.599
Gnomad MID
AF:
0.778
Gnomad NFE
AF:
0.631
Gnomad OTH
AF:
0.602
GnomAD4 exome
AF:
0.333
AC:
2
AN:
6
Hom.:
0
Cov.:
0
AF XY:
0.250
AC XY:
1
AN XY:
4
show subpopulations
Gnomad4 NFE exome
AF:
0.333
GnomAD4 genome
AF:
0.567
AC:
86262
AN:
152004
Hom.:
25797
Cov.:
32
AF XY:
0.569
AC XY:
42275
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.361
Gnomad4 AMR
AF:
0.652
Gnomad4 ASJ
AF:
0.784
Gnomad4 EAS
AF:
0.788
Gnomad4 SAS
AF:
0.673
Gnomad4 FIN
AF:
0.599
Gnomad4 NFE
AF:
0.631
Gnomad4 OTH
AF:
0.607
Alfa
AF:
0.635
Hom.:
50604
Bravo
AF:
0.569
Asia WGS
AF:
0.687
AC:
2390
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
5.3
DANN
Benign
0.38

Splicing

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: rs764255; hg19: chr16-73713683; API