rs10513356

chr3-149666500-T-Achr3-149666500-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001168278.3(WWTR1):c.-4+3288A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 152,306 control chromosomes in the GnomAD database, including 151 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 0.031 (151 hom., cov: 32)
• Consequence: WWTR1 NM_001168278.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

Genes affected

WWTR1 (HGNC:24042): (WW domain containing transcription regulator 1) Enables transcription coactivator activity. Involved in several processes, including hippo signaling; positive regulation of cell differentiation; and regulation of signal transduction. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWTR1	NM_001168278.3	c.-4+3288A>T		intron_variant
WWTR1	NM_001348362.2	c.-4+3288A>T		intron_variant
WWTR1	XM_017006122.2	c.-4+3288A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWTR1	ENST00000465804.5	c.-4+3288A>T		intron_variant		2		P1
WWTR1	ENST00000475579.1	c.-4+3288A>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4741 AN: 152188 Hom.: 151 Cov.: 32

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0281

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.0278

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

GnomAD4 genome AF: 0.0311 AC: 4740 AN: 152306 Hom.: 151 Cov.: 32 AF XY: 0.0318 AC XY: 2367 AN XY: 74472

Gnomad4 AFR AF: 0.0638

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0282

Gnomad4 FIN AF: 0.0229

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.00404 Hom.: 1

Bravo AF: 0.0320

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.8
Dann	Benign	0.57

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: rs10513356; hg19: chr3-149384287;