rs12446956

Positions:

• chr16-73467637-T-C

Variant summary

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

The ENST00000641790.1(LINC01568):​n.524-19117T>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 0.104 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: LINC01568 ENST00000641790.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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=-0.9).
• 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/exons	MANE	Protein	UniProt
ZFHX3	NM_001386735.1	c.-1063-11379A>G		intron_variant			NP_001373664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINC01568	ENST00000641790.1	n.524-19117T>C		intron_variant, non_coding_transcript_variant
ZFHX3	ENST00000641206.2	c.-1546-11379A>G		intron_variant				ENSP00000493252	P1

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

Gnomad4 AFR AF: 0.0243

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.112

Alfa AF: 0.128 Hom.: 2385

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12446956; hg19: chr16-73501536;