16-73694721-T-C

Position:

• chr16-73694721-T-C

Variant summary

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

The NM_001386735.1(ZFHX3):​c.-1124-14481A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,120 control chromosomes in the GnomAD database, including 23,252 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 0.54 (23252 hom., cov: 33)
• Consequence: ZFHX3 NM_001386735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX3	NM_001386735.1	c.-1124-14481A>G		intron_variant			NP_001373664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000641206.2	c.-1607-14481A>G		intron_variant				ENSP00000493252	P1
ZFHX3	ENST00000641018.1	n.101-14481A>G		intron_variant, non_coding_transcript_variant
ZFHX3	ENST00000642085.1	n.103-14481A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81523 AN: 152002 Hom.: 23240 Cov.: 33

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.536 AC: 81563 AN: 152120 Hom.: 23252 Cov.: 33 AF XY: 0.544 AC XY: 40489 AN XY: 74366

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.566

Alfa AF: 0.585 Hom.: 54491

Bravo AF: 0.536

Asia WGS AF: 0.686 AC: 2384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.81
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12920607; hg19: chr16-73728620;