11-102113897-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001130145.3(YAP1):c.322-247C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,704 control chromosomes in the GnomAD database, including 16,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (16383 hom., cov: 32)
• Consequence: YAP1 NM_001130145.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.117

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-102113897-C-T is Benign according to our data. Variant chr11-102113897-C-T is described in ClinVar as [Benign]. Clinvar id is 1287936.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YAP1	NM_001130145.3	c.322-247C>T		intron_variant		ENST00000282441.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YAP1	ENST00000282441.10	c.322-247C>T		intron_variant		1	NM_001130145.3	P2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68407 AN: 151586 Hom.: 16370 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.451 AC: 68452 AN: 151704 Hom.: 16383 Cov.: 32 AF XY: 0.451 AC XY: 33471 AN XY: 74148

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.470

Alfa AF: 0.516 Hom.: 25859

Bravo AF: 0.428

Asia WGS AF: 0.444 AC: 1535 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.5
Dann	Benign	0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs2033083; hg19: chr11-101984628;