rs11648088

Positions:

• chr16-73505482-A-G

Variant summary

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

The NM_001386735.1(ZFHX3):​c.-1063-49224T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,802 control chromosomes in the GnomAD database, including 6,203 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 0.25 (6203 hom., cov: 30)
• Consequence: ZFHX3 NM_001386735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX3	NM_001386735.1	c.-1063-49224T>C		intron_variant			NP_001373664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000641206.2	c.-1546-49224T>C		intron_variant				ENSP00000493252.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38094 AN: 151684 Hom.: 6201 Cov.: 30

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.251 AC: 38095 AN: 151802 Hom.: 6203 Cov.: 30 AF XY: 0.248 AC XY: 18432 AN XY: 74174

Gnomad4 AFR AF: 0.0876

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.00387

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.258

Alfa AF: 0.321 Hom.: 7761

Bravo AF: 0.230

Asia WGS AF: 0.0670 AC: 237 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11648088; hg19: chr16-73539381;