11-102157164-A-G

Variant names:

• chr11-102157164-A-G
• rs10895266
• NM_001130145.3:c.573-5292A>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.573-5292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,030 control chromosomes in the GnomAD database, including 21,102 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 0.50 (21102 hom., cov: 32)
• Consequence: YAP1 NM_001130145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.42
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YAP1	NM_001130145.3	c.573-5292A>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.573-5292A>G		intron_variant	Intron 2 of 8	1	NM_001130145.3	ENSP00000282441.5

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76109 AN: 151912 Hom.: 21054 Cov.: 32

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.501 AC: 76215 AN: 152030 Hom.: 21102 Cov.: 32 AF XY: 0.500 AC XY: 37164 AN XY: 74322

African (AFR) AF: 0.738 AC: 30604 AN: 41472

American (AMR) AF: 0.570 AC: 8700 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1101 AN: 3470

East Asian (EAS) AF: 0.470 AC: 2424 AN: 5162

South Asian (SAS) AF: 0.329 AC: 1588 AN: 4830

European-Finnish (FIN) AF: 0.416 AC: 4388 AN: 10538

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25969 AN: 67978

Other (OTH) AF: 0.487 AC: 1027 AN: 2110

Alfa AF: 0.398 Hom.: 2465

Bravo AF: 0.530

Asia WGS AF: 0.418 AC: 1454 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0070
DANN	Benign	0.46
PhyloP100		-3.4
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: rs10895266; hg19: chr11-102027895;