rs10501995

Variant names:

• chr11-102199630-A-G
• rs10501995
• NM_001130145.3:c.803-6263A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001130145.3(YAP1):​c.803-6263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 152,226 control chromosomes in the GnomAD database, including 619 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 (619 hom., cov: 32)
• Consequence: YAP1 NM_001130145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.859
• Publications: 4 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YAP1	NM_001130145.3	c.803-6263A>G		intron_variant	Intron 4 of 8	ENST00000282441.10	NP_001123617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YAP1	ENST00000282441.10	c.803-6263A>G		intron_variant	Intron 4 of 8	1	NM_001130145.3	ENSP00000282441.5

Frequencies

GnomAD3 genomes AF: 0.0841 AC: 12796 AN: 152108 Hom.: 621 Cov.: 32

Gnomad AFR AF: 0.0803

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0478

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0824

Gnomad OTH AF: 0.0771

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

GnomAD4 genome AF: 0.0840 AC: 12794 AN: 152226 Hom.: 619 Cov.: 32 AF XY: 0.0858 AC XY: 6388 AN XY: 74438

African (AFR) AF: 0.0803 AC: 3335 AN: 41522

American (AMR) AF: 0.0478 AC: 731 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3470

East Asian (EAS) AF: 0.176 AC: 911 AN: 5180

South Asian (SAS) AF: 0.204 AC: 983 AN: 4822

European-Finnish (FIN) AF: 0.0505 AC: 536 AN: 10610

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0824 AC: 5601 AN: 68008

Other (OTH) AF: 0.0768 AC: 162 AN: 2110

Alfa AF: 0.0846 Hom.: 1016

Bravo AF: 0.0813

Asia WGS AF: 0.169 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.93
PhyloP100		0.86
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10501995; hg19: chr11-102070361;