rs1477403

chr16-73389303-G-Achr16-73389303-G-Cchr16-73389303-G-T

Variant summary

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

The NR_038234.1(LINC01568):n.450+2049G>A 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 0.617 in 152,088 control chromosomes in the GnomAD database, including 29,539 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 0.62 (29539 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: LINC01568 NR_038234.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINC01568	NR_038234.1	n.450+2049G>A		intron_variant, non_coding_transcript_variant
ZFHX3	NM_001386735.1	c.-808+66700C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINC01568	ENST00000641790.1	n.431+2049G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93828 AN: 151968 Hom.: 29511 Cov.: 33

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.617 AC: 93895 AN: 152086 Hom.: 29539 Cov.: 33 AF XY: 0.611 AC XY: 45402 AN XY: 74356

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.611

Alfa AF: 0.641 Hom.: 15815

Bravo AF: 0.603

Asia WGS AF: 0.423 AC: 1471 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.8
Dann	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1477403; hg19: chr16-73423202;