rs11225163

Variant names:

• chr11-102200112-C-T
• rs11225163
• NM_001130145.3:c.803-5781C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

YAP1 Gene-Disease associations (from GenCC):

• uveal coloboma-cleft lip and palate-intellectual disability

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130145.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YAP1	NM_001130145.3	MANE Select	c.803-5781C>T		intron	N/A	NP_001123617.1	P46937-1
	YAP1	NM_001282101.2		c.803-5781C>T		intron	N/A	NP_001269030.1	P46937-9
	YAP1	NM_001282100.2		c.803-5781C>T		intron	N/A	NP_001269029.1	P46937-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YAP1	ENST00000282441.10	TSL:1 MANE Select	c.803-5781C>T		intron	N/A	ENSP00000282441.5	P46937-1
	YAP1	ENST00000531439.5	TSL:1	c.803-5781C>T		intron	N/A	ENSP00000431574.1	P46937-2
	YAP1	ENST00000951261.1		c.926-5781C>T		intron	N/A	ENSP00000621320.1

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

African (AFR) AF: 0.402 AC: 16664 AN: 41422

American (AMR) AF: 0.330 AC: 5038 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3472

East Asian (EAS) AF: 0.411 AC: 2127 AN: 5180

South Asian (SAS) AF: 0.261 AC: 1259 AN: 4828

European-Finnish (FIN) AF: 0.364 AC: 3832 AN: 10534

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23510 AN: 67988

Other (OTH) AF: 0.361 AC: 761 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.60
PhyloP100		-1.4
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: rs11225163; hg19: chr11-102070843;