chr12-69377293-G-T

Variant names:

• chr12-69377293-G-T
• rs315122
• NM_006530.4:c.514+6318G>T

Variant summary

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

The NM_006530.4(YEATS4):​c.514+6318G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,102 control chromosomes in the GnomAD database, including 44,031 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 0.76 (44031 hom., cov: 33)
• Consequence: YEATS4 NM_006530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 12 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YEATS4	NM_006530.4	c.514+6318G>T		intron_variant	Intron 6 of 6	ENST00000247843.7	NP_006521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YEATS4	ENST00000247843.7	c.514+6318G>T		intron_variant	Intron 6 of 6	1	NM_006530.4	ENSP00000247843.2
YEATS4	ENST00000548020.5	c.352+6318G>T		intron_variant	Intron 4 of 4	2		ENSP00000447199.1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115153 AN: 151984 Hom.: 43994 Cov.: 33

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.651

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.758 AC: 115244 AN: 152102 Hom.: 44031 Cov.: 33 AF XY: 0.753 AC XY: 55972 AN XY: 74346

African (AFR) AF: 0.873 AC: 36252 AN: 41532

American (AMR) AF: 0.725 AC: 11088 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 2259 AN: 3468

East Asian (EAS) AF: 0.739 AC: 3824 AN: 5172

South Asian (SAS) AF: 0.738 AC: 3556 AN: 4818

European-Finnish (FIN) AF: 0.631 AC: 6639 AN: 10516

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49179 AN: 67988

Other (OTH) AF: 0.730 AC: 1544 AN: 2114

Alfa AF: 0.740 Hom.: 84402

Bravo AF: 0.765

Asia WGS AF: 0.726 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.36
PhyloP100		-1.5
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: rs315122; hg19: chr12-69771073;