rs17681554

Positions:

• chr16-72982869-A-C
• chr16-72982869-A-G

Variant summary

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

The NM_006885.4(ZFHX3):​c.-49-22675T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,000 control chromosomes in the GnomAD database, including 11,959 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 (11959 hom., cov: 32)
• Consequence: ZFHX3 NM_006885.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.701

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX3	NM_006885.4	c.-49-22675T>G		intron_variant		ENST00000268489.10	NP_008816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000268489.10	c.-49-22675T>G		intron_variant		1	NM_006885.4	ENSP00000268489	P1
ZFHX3	ENST00000397992.5	c.-23-31904T>G		intron_variant		1		ENSP00000438926
ZFHX3	ENST00000641206.2	c.-49-22675T>G		intron_variant				ENSP00000493252	P1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59493 AN: 151882 Hom.: 11949 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.392 AC: 59539 AN: 152000 Hom.: 11959 Cov.: 32 AF XY: 0.391 AC XY: 29039 AN XY: 74318

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.407

Alfa AF: 0.407 Hom.: 24888

Bravo AF: 0.391

Asia WGS AF: 0.253 AC: 882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.0
DANN	Benign	0.57

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: rs17681554; hg19: chr16-73016768;