16-72970638-C-T

Position:

• chr16-72970638-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.-49-10444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,156 control chromosomes in the GnomAD database, including 3,842 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 0.22 (3842 hom., cov: 32)
• Consequence: ZFHX3 NM_006885.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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 = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFHX3	NM_006885.4	c.-49-10444G>A		intron_variant		ENST00000268489.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFHX3	ENST00000268489.10	c.-49-10444G>A		intron_variant		1	NM_006885.4	P1
ZFHX3	ENST00000397992.5	c.-23-19673G>A		intron_variant		1
ZFHX3	ENST00000641206.2	c.-49-10444G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32842 AN: 152038 Hom.: 3830 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0834

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.216 AC: 32882 AN: 152156 Hom.: 3842 Cov.: 32 AF XY: 0.212 AC XY: 15757 AN XY: 74404

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0833

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.198

Alfa AF: 0.208 Hom.: 4537

Bravo AF: 0.205

Asia WGS AF: 0.0560 AC: 198 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	1.6
DANN	Benign	0.74

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: rs12445917; hg19: chr16-73004537; COSMIC: COSV51738193; COSMIC: COSV51738193;