dbSNP rs16971312: ZFHX3:c.3529+7834T>C (chr16-72821945-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006885.4(ZFHX3):c.3529+7834T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0331 in 152,292 control chromosomes in the GnomAD database, including 609 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 0.033 ( 609 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZFHX3
NM_006885.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

3 publications found

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]

ZFHX3 links:

RNU7-71P (HGNC:34167): (RNA, U7 small nuclear 71 pseudogene)

RNU7-71P links:

ZFHX3-AS1 (HGNC:56033): (ZFHX3 antisense RNA 1)

ZFHX3-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006885.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZFHX3	NM_006885.4	MANE Select	c.3529+7834T>C	intron	N/A	NP_008816.3
ZFHX3	NM_001386735.1		c.3529+7834T>C	intron	N/A	NP_001373664.1
ZFHX3	NM_001164766.2		c.787+7834T>C	intron	N/A	NP_001158238.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZFHX3	ENST00000268489.10	TSL:1 MANE Select	c.3529+7834T>C	intron	N/A	ENSP00000268489.5
ZFHX3	ENST00000397992.5	TSL:1	c.787+7834T>C	intron	N/A	ENSP00000438926.3
ZFHX3	ENST00000641206.2		c.3529+7834T>C	intron	N/A	ENSP00000493252.1

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5030

AN:

152174

Hom.:

602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00586

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0256

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.0353

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0331

AC:

5042

AN:

152292

Hom.:

609

Cov.:

AF XY:

0.0371

AC XY:

2759

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00585

AC:

243

AN:

41558

American (AMR)

AF:

0.181

AC:

2775

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.282

AC:

1459

AN:

5166

South Asian (SAS)

AF:

0.0145

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0256

AC:

272

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00190

AC:

129

AN:

68026

Other (OTH)

AF:

0.0364

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

198

396

595

793

991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0441

Hom.:

147

Bravo

AF:

0.0490

Asia WGS

AF:

0.126

AC:

436

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.4

(source)

DANN

Benign

0.21

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over