dbSNP rs3811715: WWTR1:c.-107-3C>T (chr3-149669894-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001168278.3(WWTR1):c.-107-3C>T variant causes a splice region, 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, intron

Scores

Splicing: ADA: 0.00001206

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.77

Publications

6 publications found

Variant links:

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]

WWTR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	Protein	UniProt
WWTR1	NM_001168278.3 link	c.-107-3C>T	splice_region_variant, intron_variant	Intron 1 of 7	NP_001161750.1
WWTR1	NM_001348362.2 link	c.-107-3C>T	splice_region_variant, intron_variant	Intron 3 of 9	NP_001335291.1
WWTR1	XM_017006122.2 link	c.-107-3C>T	splice_region_variant, intron_variant	Intron 1 of 7	XP_016861611.1	Q9GZV5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWTR1	ENST00000465804.5 link	c.-107-3C>T		splice_region_variant, intron_variant	Intron 1 of 7	2		ENSP00000419465.1		Q9GZV5
WWTR1	ENST00000475579.1 link	c.-107-3C>T		splice_region_variant, intron_variant	Intron 1 of 2	4		ENSP00000420159.1		C9JQS8

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30143

AN:

151998

Hom.:

3233

Cov.:

show subpopulations

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:

AN:

116

Hom.:

Cov.:

AF XY:

0.186

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.146

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.198

AC:

30181

AN:

152116

Hom.:

3245

Cov.:

AF XY:

0.200

AC XY:

14908

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.203

AC:

8409

AN:

41484

American (AMR)

AF:

0.300

AC:

4584

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

402

AN:

3472

East Asian (EAS)

AF:

0.240

AC:

1242

AN:

5178

South Asian (SAS)

AF:

0.128

AC:

615

AN:

4822

European-Finnish (FIN)

AF:

0.226

AC:

2387

AN:

10578

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.177

AC:

12015

AN:

67984

Other (OTH)

AF:

0.186

AC:

394

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1207

2415

3622

4830

6037

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.192

Hom.:

5160

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

(source)

DANN

Benign

0.49

PhyloP100

-1.8

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over