12-69363649-T-C

Variant names:

• chr12-69363649-T-C
• rs6581889
• NM_006530.4:c.171+742T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 38 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=-0.84).
• 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 rank	MANE	Protein	UniProt
YEATS4	NM_006530.4	c.171+742T>C		intron_variant	Intron 2 of 6	ENST00000247843.7	NP_006521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YEATS4	ENST00000247843.7	c.171+742T>C		intron_variant	Intron 2 of 6	1	NM_006530.4	ENSP00000247843.2
YEATS4	ENST00000552955.1	c.172-528T>C		intron_variant	Intron 2 of 6	5		ENSP00000446985.1
YEATS4	ENST00000548020.5	c.171+742T>C		intron_variant	Intron 2 of 4	2		ENSP00000447199.1
YEATS4	ENST00000549685.5	c.-4+742T>C		intron_variant	Intron 3 of 6	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

African (AFR) AF: 0.305 AC: 12648 AN: 41498

American (AMR) AF: 0.420 AC: 6400 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1532 AN: 3472

East Asian (EAS) AF: 0.442 AC: 2287 AN: 5180

South Asian (SAS) AF: 0.396 AC: 1912 AN: 4828

European-Finnish (FIN) AF: 0.342 AC: 3608 AN: 10544

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31240 AN: 67958

Other (OTH) AF: 0.405 AC: 855 AN: 2112

Alfa AF: 0.441 Hom.: 41739

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
PhyloP100		1.8
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: rs6581889; hg19: chr12-69757429;