rs11225148

Variant names:

• chr11-102138549-A-G
• rs11225148
• NM_001130145.3:c.573-23907A>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.573-23907A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 152,326 control chromosomes in the GnomAD database, including 215 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 0.043 (215 hom., cov: 32)
• Consequence: YAP1 NM_001130145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YAP1	NM_001130145.3	c.573-23907A>G		intron_variant	Intron 2 of 8	ENST00000282441.10	NP_001123617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YAP1	ENST00000282441.10	c.573-23907A>G		intron_variant	Intron 2 of 8	1	NM_001130145.3	ENSP00000282441.5

Frequencies

GnomAD3 genomes AF: 0.0427 AC: 6497 AN: 152208 Hom.: 217 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0257

Gnomad EAS AF: 0.0626

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0540

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0426 AC: 6491 AN: 152326 Hom.: 215 Cov.: 32 AF XY: 0.0451 AC XY: 3356 AN XY: 74478

African (AFR) AF: 0.0106 AC: 440 AN: 41568

American (AMR) AF: 0.119 AC: 1818 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0257 AC: 89 AN: 3468

East Asian (EAS) AF: 0.0618 AC: 320 AN: 5178

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4830

European-Finnish (FIN) AF: 0.0540 AC: 573 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0442 AC: 3005 AN: 68036

Other (OTH) AF: 0.0397 AC: 84 AN: 2116

Alfa AF: 0.0439 Hom.: 629

Bravo AF: 0.0477

Asia WGS AF: 0.0360 AC: 127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.74
PhyloP100		-0.094
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: rs11225148; hg19: chr11-102009280;