chr3-149533572-A-G

Variant names:

• chr3-149533572-A-G
• rs10513355
• NM_015472.6:c.772-5603T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015472.6(WWTR1):​c.772-5603T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 152,302 control chromosomes in the GnomAD database, including 439 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 0.065 (439 hom., cov: 33)
• Consequence: WWTR1 NM_015472.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWTR1	NM_015472.6	c.772-5603T>C		intron_variant	Intron 4 of 6	ENST00000360632.8	NP_056287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWTR1	ENST00000360632.8	c.772-5603T>C		intron_variant	Intron 4 of 6	1	NM_015472.6	ENSP00000353847.3

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 9926 AN: 152184 Hom.: 439 Cov.: 33

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.0584

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.0581

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0741

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

GnomAD4 genome AF: 0.0652 AC: 9924 AN: 152302 Hom.: 439 Cov.: 33 AF XY: 0.0658 AC XY: 4897 AN XY: 74466

African (AFR) AF: 0.0174 AC: 725 AN: 41576

American (AMR) AF: 0.0583 AC: 892 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 303 AN: 3472

East Asian (EAS) AF: 0.190 AC: 983 AN: 5170

South Asian (SAS) AF: 0.0582 AC: 281 AN: 4832

European-Finnish (FIN) AF: 0.0930 AC: 987 AN: 10614

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0811 AC: 5518 AN: 68016

Other (OTH) AF: 0.0733 AC: 155 AN: 2114

Alfa AF: 0.0768 Hom.: 276

Bravo AF: 0.0625

Asia WGS AF: 0.106 AC: 370 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	4.8
DANN	Benign	0.51
PhyloP100		-0.0030
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10513355; hg19: chr3-149251359;