rs12444204

Variant names:

• chr16-73449053-T-C
• rs12444204
• NM_001386735.1:c.-808+6950A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386735.1(ZFHX3):​c.-808+6950A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,976 control chromosomes in the GnomAD database, including 30,260 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 0.58 (30260 hom., cov: 31)
• Consequence: ZFHX3 NM_001386735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.969
• Publications: 1 publications found

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]

LOHAN2 (HGNC:51371): (lncRNA oncogene in head and neck cancer 2)

ENSG00000296129 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFHX3	NM_001386735.1	c.-808+6950A>G		intron_variant	Intron 3 of 16		NP_001373664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000641206.2	c.-1291+6950A>G		intron_variant	Intron 3 of 17			ENSP00000493252.1
LOHAN2	ENST00000641790.1	n.523+28305T>C		intron_variant	Intron 2 of 3
ENSG00000296129	ENST00000736666.1	n.471+5884A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87889 AN: 151858 Hom.: 30262 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.578 AC: 87887 AN: 151976 Hom.: 30260 Cov.: 31 AF XY: 0.576 AC XY: 42751 AN XY: 74266

African (AFR) AF: 0.208 AC: 8639 AN: 41460

American (AMR) AF: 0.592 AC: 9038 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2630 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1449 AN: 5148

South Asian (SAS) AF: 0.705 AC: 3392 AN: 4812

European-Finnish (FIN) AF: 0.713 AC: 7522 AN: 10546

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53045 AN: 67970

Other (OTH) AF: 0.603 AC: 1273 AN: 2112

Alfa AF: 0.659 Hom.: 4805

Bravo AF: 0.547

Asia WGS AF: 0.464 AC: 1616 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	5.3
DANN	Benign	0.56
PhyloP100		0.97

Splicing

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

Other links and lift over

dbSNP: rs12444204; hg19: chr16-73482952;