chr16-73405456-C-T

Variant names:

• chr16-73405456-C-T
• rs9934948
• ENST00000555721.2:n.455-14643C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000555721.2(LOHAN2):​n.455-14643C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,068 control chromosomes in the GnomAD database, including 6,432 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 0.26 (6432 hom., cov: 32)
• Consequence: LOHAN2 ENST00000555721.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 22 publications found

Genes affected

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

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]

ZFHX3 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Broad Center for Mendelian Genomics
• spinocerebellar ataxia type 4

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFHX3	NM_001386735.1	c.-808+50547G>A		intron_variant	Intron 3 of 16		NP_001373664.1
LOHAN2	NR_038234.1	n.451-14637C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOHAN2	ENST00000555721.2	n.455-14643C>T		intron_variant	Intron 1 of 2	1
ZFHX3	ENST00000641206.2	c.-1291+50547G>A		intron_variant	Intron 3 of 17			ENSP00000493252.1
LOHAN2	ENST00000562661.1	n.203-15201C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39455 AN: 151948 Hom.: 6412 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.260 AC: 39523 AN: 152068 Hom.: 6432 Cov.: 32 AF XY: 0.266 AC XY: 19792 AN XY: 74342

African (AFR) AF: 0.407 AC: 16882 AN: 41462

American (AMR) AF: 0.291 AC: 4454 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 494 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2871 AN: 5166

South Asian (SAS) AF: 0.416 AC: 2007 AN: 4824

European-Finnish (FIN) AF: 0.180 AC: 1902 AN: 10562

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.148 AC: 10082 AN: 67988

Other (OTH) AF: 0.254 AC: 535 AN: 2110

Alfa AF: 0.188 Hom.: 13995

Bravo AF: 0.272

Asia WGS AF: 0.450 AC: 1561 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Benign	0.75
PhyloP100		2.1

Splicing

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

Other links and lift over

dbSNP: rs9934948; hg19: chr16-73439355; COSMIC: COSV73529036;