chr16-73805897-G-A

Position:

• chr16-73805897-G-A

Variant summary

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

The NM_001386735.1(ZFHX3):​c.-1125+85754C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,036 control chromosomes in the GnomAD database, including 12,151 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 0.39 (12151 hom., cov: 32)
• Consequence: ZFHX3 NM_001386735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670

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]

ENSG00000283457 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX3	NM_001386735.1	c.-1125+85754C>T		intron_variant			NP_001373664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000641206.2	c.-1608+85754C>T		intron_variant				ENSP00000493252.1
ENSG00000283457	ENST00000637695.1	n.425-2575G>A		intron_variant		5
ZFHX3	ENST00000641018.1	n.100+85754C>T		intron_variant
ZFHX3	ENST00000642085.1	n.102+85754C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59813 AN: 151916 Hom.: 12135 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.394 AC: 59876 AN: 152036 Hom.: 12151 Cov.: 32 AF XY: 0.393 AC XY: 29190 AN XY: 74312

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.395

Alfa AF: 0.368 Hom.: 1527

Bravo AF: 0.400

Asia WGS AF: 0.435 AC: 1512 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	1.2
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs328384; hg19: chr16-73839796;