rs3811715

chr3-149669894-G-A

Variant summary

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

The NM_001168278.3(WWTR1):c.-107-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,232 control chromosomes in the GnomAD database, including 3,247 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3245 hom., cov: 32)
  • Exomes 𝑓: 0.17 (2 hom.)
• Consequence: WWTR1 NM_001168278.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001206
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWTR1	NM_001168278.3	c.-107-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
WWTR1	NM_001348362.2	c.-107-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
WWTR1	XM_017006122.2	c.-107-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWTR1	ENST00000465804.5	c.-107-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		P1
WWTR1	ENST00000475579.1	c.-107-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30143 AN: 151998 Hom.: 3233 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.172 AC: 20 AN: 116 Hom.: 2 Cov.: 0 AF XY: 0.186 AC XY: 16 AN XY: 86

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.198 AC: 30181 AN: 152116 Hom.: 3245 Cov.: 32 AF XY: 0.200 AC XY: 14908 AN XY: 74372

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.186

Alfa AF: 0.186 Hom.: 2821

Bravo AF: 0.211

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.13
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.14		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: rs3811715; hg19: chr3-149387681;