rs11075958

chr16-72999970-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.-49-39776G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,220 control chromosomes in the GnomAD database, including 1,934 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 0.14 (1934 hom., cov: 33)
• Consequence: ZFHX3 NM_006885.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFHX3	NM_006885.4	c.-49-39776G>A		intron_variant		ENST00000268489.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFHX3	ENST00000268489.10	c.-49-39776G>A		intron_variant		1	NM_006885.4	P1
ZFHX3	ENST00000397992.5	c.-23-49005G>A		intron_variant		1
ZFHX3	ENST00000641206.2	c.-49-39776G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20616 AN: 152102 Hom.: 1934 Cov.: 33

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0908

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.135 AC: 20610 AN: 152220 Hom.: 1934 Cov.: 33 AF XY: 0.134 AC XY: 9957 AN XY: 74408

Gnomad4 AFR AF: 0.0369

Gnomad4 AMR AF: 0.0906

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0610

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.127

Alfa AF: 0.149 Hom.: 452

Bravo AF: 0.120

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.1
Dann	Benign	0.50

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: rs11075958; hg19: chr16-73033869;