chr12-69368429-T-C

Variant names:

• chr12-69368429-T-C
• rs17106480
• NM_006530.4:c.334-2277T>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.334-2277T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0244 in 152,310 control chromosomes in the GnomAD database, including 143 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 0.024 (143 hom., cov: 32)
• Consequence: YEATS4 NM_006530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656
• 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YEATS4	NM_006530.4	c.334-2277T>C		intron_variant	Intron 4 of 6	ENST00000247843.7	NP_006521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YEATS4	ENST00000247843.7	c.334-2277T>C		intron_variant	Intron 4 of 6	1	NM_006530.4	ENSP00000247843.2
YEATS4	ENST00000552955.1	c.457-2277T>C		intron_variant	Intron 5 of 6	5		ENSP00000446985.1
YEATS4	ENST00000548020.5	c.172-2277T>C		intron_variant	Intron 2 of 4	2		ENSP00000447199.1
YEATS4	ENST00000549685.5	c.160-2277T>C		intron_variant	Intron 5 of 6	5		ENSP00000448106.1

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3714 AN: 152192 Hom.: 144 Cov.: 32

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.0205

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

GnomAD4 genome AF: 0.0244 AC: 3717 AN: 152310 Hom.: 143 Cov.: 32 AF XY: 0.0236 AC XY: 1755 AN XY: 74486

African (AFR) AF: 0.0836 AC: 3475 AN: 41560

American (AMR) AF: 0.0103 AC: 158 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68012

Other (OTH) AF: 0.0203 AC: 43 AN: 2116

Alfa AF: 0.0207 Hom.: 11

Bravo AF: 0.0280

Asia WGS AF: 0.00607 AC: 21 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.6
DANN	Benign	0.92
PhyloP100		-0.66
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: rs17106480; hg19: chr12-69762209;