12-69363649-T-C

Position:

• chr12-69363649-T-C

Variant summary

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

The NM_006530.4(YEATS4):​c.171+742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,044 control chromosomes in the GnomAD database, including 12,566 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 (12566 hom., cov: 32)
• Consequence: YEATS4 NM_006530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84

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]

YEATS4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YEATS4	NM_006530.4	c.171+742T>C		intron_variant		ENST00000247843.7	NP_006521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YEATS4	ENST00000247843.7	c.171+742T>C		intron_variant		1	NM_006530.4	ENSP00000247843.2
YEATS4	ENST00000552955.1	c.172-528T>C		intron_variant		5		ENSP00000446985.1
YEATS4	ENST00000548020.5	c.171+742T>C		intron_variant		2		ENSP00000447199.1
YEATS4	ENST00000549685.5	c.-4+742T>C		intron_variant		5		ENSP00000448106.1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 61036 AN: 151924 Hom.: 12558 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.402 AC: 61054 AN: 152044 Hom.: 12566 Cov.: 32 AF XY: 0.397 AC XY: 29461 AN XY: 74294

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.405

Alfa AF: 0.445 Hom.: 29608

Bravo AF: 0.402

Asia WGS AF: 0.344 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.79

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: rs6581889; hg19: chr12-69757429;