11-102199908-A-G

Variant names:

• chr11-102199908-A-G
• rs1894116
• NM_001130145.3:c.803-5985A>G

Variant summary

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

The NM_001130145.3(YAP1):​c.803-5985A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 152,304 control chromosomes in the GnomAD database, including 622 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 0.084 (622 hom., cov: 32)
• Consequence: YAP1 NM_001130145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 33 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YAP1	NM_001130145.3	MANE Select	c.803-5985A>G		intron	N/A	NP_001123617.1
	YAP1	NM_001282101.2		c.803-5985A>G		intron	N/A	NP_001269030.1
	YAP1	NM_001282100.2		c.803-5985A>G		intron	N/A	NP_001269029.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YAP1	ENST00000282441.10	TSL:1 MANE Select	c.803-5985A>G		intron	N/A	ENSP00000282441.5
	YAP1	ENST00000531439.5	TSL:1	c.803-5985A>G		intron	N/A	ENSP00000431574.1
	YAP1	ENST00000615667.4	TSL:5	c.803-5985A>G		intron	N/A	ENSP00000478927.1

Frequencies

GnomAD3 genomes AF: 0.0842 AC: 12819 AN: 152186 Hom.: 624 Cov.: 32

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0477

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0822

Gnomad OTH AF: 0.0774

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

GnomAD4 genome AF: 0.0841 AC: 12815 AN: 152304 Hom.: 622 Cov.: 32 AF XY: 0.0858 AC XY: 6392 AN XY: 74472

African (AFR) AF: 0.0808 AC: 3358 AN: 41570

American (AMR) AF: 0.0476 AC: 729 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3466

East Asian (EAS) AF: 0.177 AC: 919 AN: 5180

South Asian (SAS) AF: 0.204 AC: 985 AN: 4828

European-Finnish (FIN) AF: 0.0504 AC: 535 AN: 10620

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0822 AC: 5593 AN: 68020

Other (OTH) AF: 0.0770 AC: 163 AN: 2116

Alfa AF: 0.0860 Hom.: 2045

Bravo AF: 0.0813

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.79
PhyloP100		1.1
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: rs1894116; hg19: chr11-102070639;