16-73051387-A-G

Position:

• chr16-73051387-A-G

Variant summary

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

The NM_001386735.1(ZFHX3):​c.-50+41848T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,006 control chromosomes in the GnomAD database, including 9,769 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 0.33 (9769 hom., cov: 32)
• Consequence: ZFHX3 NM_001386735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.708

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFHX3	NM_001386735.1	c.-50+41848T>C		intron_variant			NP_001373664.1
ZFHX3	NM_001164766.2	c.-24+7143T>C		intron_variant			NP_001158238.1
ZFHX3	XM_047434166.1	c.-50+41848T>C		intron_variant			XP_047290122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000397992.5	c.-24+7143T>C		intron_variant		1		ENSP00000438926.3
ZFHX3	ENST00000641206.2	c.-50+7143T>C		intron_variant				ENSP00000493252.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49879 AN: 151884 Hom.: 9749 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.329 AC: 49953 AN: 152006 Hom.: 9769 Cov.: 32 AF XY: 0.324 AC XY: 24116 AN XY: 74322

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.336

Alfa AF: 0.240 Hom.: 4397

Bravo AF: 0.341

Asia WGS AF: 0.349 AC: 1212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.9
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8049936; hg19: chr16-73085286;