12-69369207-A-G

Variant names:

• chr12-69369207-A-G
• rs315135
• NM_006530.4:c.334-1499A>G

Variant summary

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

The NM_006530.4(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 NM_006530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 23 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006530.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YEATS4	NM_006530.4	MANE Select	c.334-1499A>G		intron	N/A	NP_006521.1
	YEATS4	NM_001300950.2		c.172-1499A>G		intron	N/A	NP_001287879.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YEATS4	ENST00000247843.7	TSL:1 MANE Select	c.334-1499A>G		intron	N/A	ENSP00000247843.2
	YEATS4	ENST00000552955.1	TSL:5	c.457-1499A>G		intron	N/A	ENSP00000446985.1
	YEATS4	ENST00000548020.5	TSL:2	c.172-1499A>G		intron	N/A	ENSP00000447199.1

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

African (AFR) AF: 0.120 AC: 4965 AN: 41530

American (AMR) AF: 0.0439 AC: 672 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0583 AC: 202 AN: 3462

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0155 AC: 75 AN: 4830

European-Finnish (FIN) AF: 0.0111 AC: 118 AN: 10614

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0418 AC: 2843 AN: 68026

Other (OTH) AF: 0.0512 AC: 108 AN: 2108

Alfa AF: 0.0488 Hom.: 486

Bravo AF: 0.0653

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.71
PhyloP100		0.23
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: rs315135; hg19: chr12-69762987;