chr16-72948050-C-A

Position:

• chr16-72948050-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006885.4(ZFHX3):​c.3216+2419G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,030 control chromosomes in the GnomAD database, including 26,657 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 0.58 (26657 hom., cov: 32)
• Consequence: ZFHX3 NM_006885.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFHX3	NM_006885.4	c.3216+2419G>T		intron_variant		ENST00000268489.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFHX3	ENST00000268489.10	c.3216+2419G>T		intron_variant		1	NM_006885.4	P1
ZFHX3	ENST00000397992.5	c.474+2419G>T		intron_variant		1
ZFHX3	ENST00000641206.2	c.3216+2419G>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88609 AN: 151912 Hom.: 26638 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.583 AC: 88654 AN: 152030 Hom.: 26657 Cov.: 32 AF XY: 0.586 AC XY: 43521 AN XY: 74308

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.606

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.615

Alfa AF: 0.624 Hom.: 9745

Bravo AF: 0.585

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.035
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs13336412; hg19: chr16-72981949;