chr12-69391968-A-G

Position:

• chr12-69391968-A-G

Variant summary

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

The XR_944742.4(YEATS4):​n.745-15192A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,042 control chromosomes in the GnomAD database, including 12,359 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 0.40 (12359 hom., cov: 32)
• Consequence: YEATS4 XR_944742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47

Genes affected

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YEATS4	XR_001748876.2	n.745-15192A>G		intron_variant
YEATS4	XR_007063126.1	n.745-15192A>G		intron_variant
YEATS4	XR_007063128.1	n.745-15192A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60343 AN: 151924 Hom.: 12353 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.397 AC: 60357 AN: 152042 Hom.: 12359 Cov.: 32 AF XY: 0.392 AC XY: 29129 AN XY: 74316

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.401

Alfa AF: 0.434 Hom.: 3632

Bravo AF: 0.396

Asia WGS AF: 0.344 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.043
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11177644; hg19: chr12-69785748;