rs315135

Positions:

• chr12-69369207-A-G

Variant summary

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

The ENST00000247843.7(YEATS4):​c.334-1499A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0592 in 152,262 control chromosomes in the GnomAD database, including 393 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 0.059 (393 hom., cov: 32)
• Consequence: YEATS4 ENST00000247843.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YEATS4	NM_006530.4	c.334-1499A>G		intron_variant		ENST00000247843.7	NP_006521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YEATS4	ENST00000247843.7	c.334-1499A>G		intron_variant		1	NM_006530.4	ENSP00000247843	P1
YEATS4	ENST00000548020.5	c.172-1499A>G		intron_variant		2		ENSP00000447199
YEATS4	ENST00000549685.5	c.160-1499A>G		intron_variant		5		ENSP00000448106
YEATS4	ENST00000552955.1	c.457-1499A>G		intron_variant		5		ENSP00000446985

Frequencies

GnomAD3 genomes AF: 0.0592 AC: 9009 AN: 152144 Hom.: 391 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0441

Gnomad ASJ AF: 0.0583

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0111

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0518

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

GnomAD4 genome AF: 0.0592 AC: 9019 AN: 152262 Hom.: 393 Cov.: 32 AF XY: 0.0569 AC XY: 4237 AN XY: 74460

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.0583

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0155

Gnomad4 FIN AF: 0.0111

Gnomad4 NFE AF: 0.0418

Gnomad4 OTH AF: 0.0512

Alfa AF: 0.0471 Hom.: 321

Bravo AF: 0.0653

Asia WGS AF: 0.0160 AC: 56 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	1.6
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs315135; hg19: chr12-69762987;