NM_001386735.1:c.-1063-11379A>G

Variant names:

• chr16-73467637-T-C
• rs12446956
• NM_001386735.1:c.-1063-11379A>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.-1063-11379A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,216 control chromosomes in the GnomAD database, including 1,146 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 0.10 (1146 hom., cov: 32)
• Consequence: ZFHX3 NM_001386735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 13 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFHX3	NM_001386735.1	c.-1063-11379A>G		intron_variant	Intron 2 of 16		NP_001373664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFHX3	ENST00000641206.2	c.-1546-11379A>G		intron_variant	Intron 2 of 17			ENSP00000493252.1
LOHAN2	ENST00000641790.1	n.524-19117T>C		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15794 AN: 152098 Hom.: 1147 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.104 AC: 15788 AN: 152216 Hom.: 1146 Cov.: 32 AF XY: 0.107 AC XY: 7991 AN XY: 74424

African (AFR) AF: 0.0243 AC: 1008 AN: 41552

American (AMR) AF: 0.119 AC: 1819 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 630 AN: 3472

East Asian (EAS) AF: 0.251 AC: 1297 AN: 5168

South Asian (SAS) AF: 0.276 AC: 1331 AN: 4814

European-Finnish (FIN) AF: 0.102 AC: 1080 AN: 10594

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8289 AN: 68010

Other (OTH) AF: 0.112 AC: 236 AN: 2110

Alfa AF: 0.121 Hom.: 3391

Bravo AF: 0.0975

Asia WGS AF: 0.255 AC: 885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.68
PhyloP100		0.055

Splicing

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

Other links and lift over

dbSNP: rs12446956; hg19: chr16-73501536;