12-69361865-G-A

Variant names:

• chr12-69361865-G-A
• rs12371475
• NM_006530.4:c.52-923G>A

Variant summary

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

The NM_006530.4(YEATS4):​c.52-923G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,168 control chromosomes in the GnomAD database, including 1,548 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 0.13 (1548 hom., cov: 33)
• Consequence: YEATS4 NM_006530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.739
• Publications: 0 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YEATS4	NM_006530.4	c.52-923G>A		intron_variant	Intron 1 of 6	ENST00000247843.7	NP_006521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YEATS4	ENST00000247843.7	c.52-923G>A		intron_variant	Intron 1 of 6	1	NM_006530.4	ENSP00000247843.2

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19219 AN: 152052 Hom.: 1549 Cov.: 33

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.126 AC: 19216 AN: 152168 Hom.: 1548 Cov.: 33 AF XY: 0.127 AC XY: 9469 AN XY: 74388

African (AFR) AF: 0.0353 AC: 1465 AN: 41520

American (AMR) AF: 0.106 AC: 1620 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3472

East Asian (EAS) AF: 0.0152 AC: 79 AN: 5188

South Asian (SAS) AF: 0.0837 AC: 404 AN: 4824

European-Finnish (FIN) AF: 0.245 AC: 2583 AN: 10550

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12195 AN: 68012

Other (OTH) AF: 0.122 AC: 257 AN: 2114

Alfa AF: 0.152 Hom.: 270

Bravo AF: 0.110

Asia WGS AF: 0.0400 AC: 139 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.3
DANN	Benign	0.37
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12371475; hg19: chr12-69755645;