rs719353

Positions:

• chr16-73008652-G-A

Variant summary

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

The NM_006885.4(ZFHX3):​c.-50+39100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,924 control chromosomes in the GnomAD database, including 26,553 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 (26553 hom., cov: 31)
• Consequence: ZFHX3 NM_006885.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFHX3	NM_006885.4	c.-50+39100C>T		intron_variant		ENST00000268489.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFHX3	ENST00000268489.10	c.-50+39100C>T		intron_variant		1	NM_006885.4	P1
ZFHX3	ENST00000397992.5	c.-24+49878C>T		intron_variant		1
ZFHX3	ENST00000641206.2	c.-49-48458C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86739 AN: 151808 Hom.: 26506 Cov.: 31

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.572 AC: 86839 AN: 151924 Hom.: 26553 Cov.: 31 AF XY: 0.577 AC XY: 42826 AN XY: 74270

Gnomad4 AFR AF: 0.774

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.555

Alfa AF: 0.466 Hom.: 29546

Bravo AF: 0.595

Asia WGS AF: 0.679 AC: 2359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	9.7
DANN	Benign	0.28

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: rs719353; hg19: chr16-73042551;