rs8055870

Positions:

• chr16-72938191-A-G
• chr16-72938191-A-T

Variant summary

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

The NM_006885.4(ZFHX3):​c.3216+12278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,278 control chromosomes in the GnomAD database, including 33,808 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 0.65 (33808 hom., cov: 35)
• Consequence: ZFHX3 NM_006885.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX3	NM_006885.4	c.3216+12278T>C		intron_variant		ENST00000268489.10	NP_008816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000268489.10	c.3216+12278T>C		intron_variant		1	NM_006885.4	ENSP00000268489	P1
ZFHX3	ENST00000397992.5	c.474+12278T>C		intron_variant		1		ENSP00000438926
ZFHX3	ENST00000641206.2	c.3216+12278T>C		intron_variant				ENSP00000493252	P1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98862 AN: 152160 Hom.: 33758 Cov.: 35

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.650 AC: 98973 AN: 152278 Hom.: 33808 Cov.: 35 AF XY: 0.654 AC XY: 48698 AN XY: 74454

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.642

Alfa AF: 0.561 Hom.: 50104

Bravo AF: 0.667

Asia WGS AF: 0.779 AC: 2703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.66

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: rs8055870; hg19: chr16-72972090;