rs17787940

Positions:

• chr3-149532802-T-C

Variant summary

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

The NM_015472.6(WWTR1):​c.772-4833A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0767 in 152,158 control chromosomes in the GnomAD database, including 544 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 0.077 (544 hom., cov: 33)
• Consequence: WWTR1 NM_015472.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWTR1	NM_015472.6	c.772-4833A>G		intron_variant		ENST00000360632.8	NP_056287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWTR1	ENST00000360632.8	c.772-4833A>G		intron_variant		1	NM_015472.6	ENSP00000353847	P1

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11662 AN: 152040 Hom.: 542 Cov.: 33

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.0693

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.0699

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.0904

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

GnomAD4 genome AF: 0.0767 AC: 11666 AN: 152158 Hom.: 544 Cov.: 33 AF XY: 0.0756 AC XY: 5626 AN XY: 74374

Gnomad4 AFR AF: 0.0266

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.0571

Gnomad4 EAS AF: 0.0691

Gnomad4 SAS AF: 0.0758

Gnomad4 FIN AF: 0.0699

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.0895

Alfa AF: 0.0901 Hom.: 345

Bravo AF: 0.0807

Asia WGS AF: 0.0710 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.74
DANN	Benign	0.41

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: rs17787940; hg19: chr3-149250589;