11-102110546-T-C

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.-303T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 190,512 control chromosomes in the GnomAD database, including 30,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (25020 hom., cov: 33)
  • Exomes 𝑓: 0.50 (5056 hom.)
• Consequence: YAP1 NM_001130145.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.78

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=-0.84).
• BP6: Variant 11-102110546-T-C is Benign according to our data. Variant chr11-102110546-T-C is described in ClinVar as [Benign]. Clinvar id is 1278207.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YAP1	NM_001130145.3	c.-303T>C		5_prime_UTR_variant	1/9	ENST00000282441.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YAP1	ENST00000282441.10	c.-303T>C		5_prime_UTR_variant	1/9	1	NM_001130145.3	P2

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85034 AN: 151788 Hom.: 24984 Cov.: 33

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.551

GnomAD4 exome AF: 0.502 AC: 19368 AN: 38616 Hom.: 5056 Cov.: 0 AF XY: 0.493 AC XY: 10234 AN XY: 20774

Gnomad4 AFR exome AF: 0.774

Gnomad4 AMR exome AF: 0.644

Gnomad4 ASJ exome AF: 0.404

Gnomad4 EAS exome AF: 0.755

Gnomad4 SAS exome AF: 0.435

Gnomad4 FIN exome AF: 0.477

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.514

GnomAD4 genome AF: 0.560 AC: 85115 AN: 151896 Hom.: 25020 Cov.: 33 AF XY: 0.561 AC XY: 41640 AN XY: 74280

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.544

Alfa AF: 0.518 Hom.: 3342

Bravo AF: 0.584

Asia WGS AF: 0.586 AC: 2028 AN: 3462

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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.40
Dann	Benign	0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7106388; hg19: chr11-101981277;