16-73017721-C-T

Position:

• chr16-73017721-C-T

Variant summary

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

The NM_006885.4(ZFHX3):​c.-50+30031G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,850 control chromosomes in the GnomAD database, including 3,600 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 0.21 (3600 hom., cov: 30)
• Consequence: ZFHX3 NM_006885.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695

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 (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX3	NM_006885.4	c.-50+30031G>A		intron_variant		ENST00000268489.10	NP_008816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000268489.10	c.-50+30031G>A		intron_variant		1	NM_006885.4	ENSP00000268489.5
ZFHX3	ENST00000397992.5	c.-24+40809G>A		intron_variant		1		ENSP00000438926.3
ZFHX3	ENST00000641206.2	c.-50+40809G>A		intron_variant				ENSP00000493252.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31976 AN: 151732 Hom.: 3596 Cov.: 30

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.211 AC: 31998 AN: 151850 Hom.: 3600 Cov.: 30 AF XY: 0.216 AC XY: 16005 AN XY: 74198

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.180

Alfa AF: 0.171 Hom.: 4754

Bravo AF: 0.210

Asia WGS AF: 0.254 AC: 883 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	6.1
DANN	Benign	0.39

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: rs2106261; hg19: chr16-73051620; COSMIC: COSV51738048; COSMIC: COSV51738048;