12-69416428-C-T

Variant names:

• chr12-69416428-C-T
• rs17225223
• ENST00000776073.1:n.246-7573C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000776073.1(LINC02373):​n.246-7573C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,128 control chromosomes in the GnomAD database, including 1,213 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 0.12 (1213 hom., cov: 32)
• Consequence: LINC02373 ENST00000776073.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 4 publications found

Genes affected

LINC02373 (HGNC:53295): (long intergenic non-protein coding RNA 2373)

YEATS4 (HGNC:24859): (YEATS domain containing 4) The protein encoded by this gene is found in the nucleoli. It has high sequence homology to human MLLT1, and yeast and human MLLT3 proteins. Both MLLT1 and MLLT3 proteins belong to a class of transcription factors, indicating that the encoded protein might also represent a transcription factor. This protein is thought to be required for RNA transcription. This gene has been shown to be amplified in tumors. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YEATS4	XR_944742.4	n.860-7573C>T		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC02373	ENST00000776073.1	n.246-7573C>T		intron_variant	Intron 2 of 4
LINC02373	ENST00000776080.1	n.-31C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17544 AN: 152010 Hom.: 1213 Cov.: 32

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.115 AC: 17536 AN: 152128 Hom.: 1213 Cov.: 32 AF XY: 0.120 AC XY: 8926 AN XY: 74372

African (AFR) AF: 0.0347 AC: 1440 AN: 41506

American (AMR) AF: 0.144 AC: 2201 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3468

East Asian (EAS) AF: 0.192 AC: 992 AN: 5168

South Asian (SAS) AF: 0.145 AC: 699 AN: 4814

European-Finnish (FIN) AF: 0.217 AC: 2290 AN: 10568

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 9003 AN: 68000

Other (OTH) AF: 0.120 AC: 253 AN: 2110

Alfa AF: 0.125 Hom.: 3997

Bravo AF: 0.104

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.8
DANN	Benign	0.75
PhyloP100		-0.0060

Splicing

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

Other links and lift over

dbSNP: rs17225223; hg19: chr12-69810208;