3-149601710-ATTTTT-ATTT

Variant names:

• chr3-149601710-ATT-A
• rs3976504
• NM_015472.6:c.432-28712_432-28711delAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_015472.6(WWTR1):​c.432-28712_432-28711delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0083 (19 hom., cov: 0)
• Consequence: WWTR1 NM_015472.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• Publications: 0 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00827 (1246/150728) while in subpopulation AFR AF = 0.0276 (1138/41170). AF 95% confidence interval is 0.0263. There are 19 homozygotes in GnomAd4. There are 632 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1246 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWTR1	NM_015472.6	c.432-28712_432-28711delAA		intron_variant	Intron 2 of 6	ENST00000360632.8	NP_056287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWTR1	ENST00000360632.8	c.432-28712_432-28711delAA		intron_variant	Intron 2 of 6	1	NM_015472.6	ENSP00000353847.3
WWTR1	ENST00000465804.5	c.432-28712_432-28711delAA		intron_variant	Intron 3 of 7	2		ENSP00000419465.1
WWTR1	ENST00000467467.5	c.432-28712_432-28711delAA		intron_variant	Intron 2 of 6	5		ENSP00000419234.1
WWTR1	ENST00000479238.1	c.432-28712_432-28711delAA		intron_variant	Intron 1 of 1	3		ENSP00000418580.1

Frequencies

GnomAD3 genomes AF: 0.00824 AC: 1241 AN: 150614 Hom.: 19 Cov.: 0

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00356

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00168

Gnomad FIN AF: 0.0000990

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000385

Gnomad OTH AF: 0.00674

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

GnomAD4 genome AF: 0.00827 AC: 1246 AN: 150728 Hom.: 19 Cov.: 0 AF XY: 0.00858 AC XY: 632 AN XY: 73648

African (AFR) AF: 0.0276 AC: 1138 AN: 41170

American (AMR) AF: 0.00356 AC: 54 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3460

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5158

South Asian (SAS) AF: 0.00168 AC: 8 AN: 4760

European-Finnish (FIN) AF: 0.0000990 AC: 1 AN: 10106

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000385 AC: 26 AN: 67586

Other (OTH) AF: 0.00667 AC: 14 AN: 2100

Alfa AF: 0.00 Hom.: 1335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs3976504; hg19: chr3-149319497;