rs12444204

chr16-73449053-T-C

Variant summary

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

The ENST00000641790.1(LINC01568):n.523+28305T>C variant causes a intron, non coding transcript 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: LINC01568 ENST00000641790.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.969

Genes affected

LINC01568 (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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ZFHX3	NM_001386735.1	c.-808+6950A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINC01568	ENST00000641790.1	n.523+28305T>C		intron_variant, non_coding_transcript_variant
ZFHX3	ENST00000641206.2	c.-1291+6950A>G		intron_variant				P1

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

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.603

Alfa AF: 0.678 Hom.: 4787

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12444204; hg19: chr16-73482952;