rs11225163

Positions:

• chr11-102200112-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001130145.3(YAP1):​c.803-5781C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,018 control chromosomes in the GnomAD database, including 10,023 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 0.36 (10023 hom., cov: 33)
• Consequence: YAP1 NM_001130145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

Genes affected

YAP1 (HGNC:16262): (Yes1 associated transcriptional regulator) This gene encodes a downstream nuclear effector of the Hippo signaling pathway which is involved in development, growth, repair, and homeostasis. This gene is known to play a role in the development and progression of multiple cancers as a transcriptional regulator of this signaling pathway and may function as a potential target for cancer treatment. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YAP1	NM_001130145.3	c.803-5781C>T		intron_variant		ENST00000282441.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YAP1	ENST00000282441.10	c.803-5781C>T		intron_variant		1	NM_001130145.3	P2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54523 AN: 151900 Hom.: 9997 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.359 AC: 54590 AN: 152018 Hom.: 10023 Cov.: 33 AF XY: 0.358 AC XY: 26598 AN XY: 74300

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.361

Alfa AF: 0.346 Hom.: 1167

Bravo AF: 0.363

Asia WGS AF: 0.329 AC: 1148 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	1.5
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs11225163; hg19: chr11-102070843;