rs899884

Positions:

• chr16-73690389-A-C
• chr16-73690389-A-G
• chr16-73690389-A-T

Variant summary

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

The NM_001386735.1(ZFHX3):​c.-1124-10149T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,190 control chromosomes in the GnomAD database, including 61,632 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 0.89 (61632 hom., cov: 32)
• Consequence: ZFHX3 NM_001386735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.226

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFHX3	NM_001386735.1	c.-1124-10149T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFHX3	ENST00000641206.2	c.-1607-10149T>G		intron_variant				P1
ZFHX3	ENST00000641018.1	n.101-10149T>G		intron_variant, non_coding_transcript_variant
ZFHX3	ENST00000642085.1	n.103-10149T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135596 AN: 152072 Hom.: 61596 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.972

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.892 AC: 135686 AN: 152190 Hom.: 61632 Cov.: 32 AF XY: 0.894 AC XY: 66518 AN XY: 74414

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.942

Gnomad4 ASJ AF: 0.972

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.924

Gnomad4 FIN AF: 0.985

Gnomad4 NFE AF: 0.965

Gnomad4 OTH AF: 0.905

Alfa AF: 0.953 Hom.: 32353

Bravo AF: 0.881

Asia WGS AF: 0.931 AC: 3238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs899884; hg19: chr16-73724288;