chr16-72945144-C-G

Variant summary

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

The NM_006885.4(ZFHX3):​c.3216+5325G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,864 control chromosomes in the GnomAD database, including 3,724 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 0.18 ( 3724 hom., cov: 32)

Consequence

ZFHX3
NM_006885.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.850
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=-0.98).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZFHX3NM_006885.4 linkuse as main transcriptc.3216+5325G>C intron_variant ENST00000268489.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZFHX3ENST00000268489.10 linkuse as main transcriptc.3216+5325G>C intron_variant 1 NM_006885.4 P1Q15911-1
ZFHX3ENST00000397992.5 linkuse as main transcriptc.474+5325G>C intron_variant 1 Q15911-2
ZFHX3ENST00000641206.2 linkuse as main transcriptc.3216+5325G>C intron_variant P1Q15911-1

Frequencies

GnomAD3 genomes
AF:
0.183
AC:
27744
AN:
151746
Hom.:
3722
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.307
Gnomad AMI
AF:
0.0526
Gnomad AMR
AF:
0.127
Gnomad ASJ
AF:
0.120
Gnomad EAS
AF:
0.596
Gnomad SAS
AF:
0.261
Gnomad FIN
AF:
0.169
Gnomad MID
AF:
0.123
Gnomad NFE
AF:
0.0914
Gnomad OTH
AF:
0.158
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.183
AC:
27779
AN:
151864
Hom.:
3724
Cov.:
32
AF XY:
0.191
AC XY:
14182
AN XY:
74190
show subpopulations
Gnomad4 AFR
AF:
0.307
Gnomad4 AMR
AF:
0.127
Gnomad4 ASJ
AF:
0.120
Gnomad4 EAS
AF:
0.595
Gnomad4 SAS
AF:
0.261
Gnomad4 FIN
AF:
0.169
Gnomad4 NFE
AF:
0.0914
Gnomad4 OTH
AF:
0.156
Alfa
AF:
0.0527
Hom.:
65
Bravo
AF:
0.184
Asia WGS
AF:
0.412
AC:
1428
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
0.21
DANN
Benign
0.25

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: rs12596992; hg19: chr16-72979043; API