dbSNP rs3811715: WWTR1:c.-110C>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. Variant has been reported in ClinVar as (no stars).

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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168278.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WWTR1	NM_001168278.3		c.-107-3C>T		splice_region intron	N/A	NP_001161750.1	Q9GZV5
	WWTR1	NM_001348362.2		c.-107-3C>T		splice_region intron	N/A	NP_001335291.1	Q9GZV5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WWTR1	ENST00000884350.1		c.-110C>T	5_prime_UTR	Exon 1 of 7	ENSP00000554409.1
WWTR1	ENST00000465804.5	TSL:2	c.-107-3C>T	splice_region intron	N/A	ENSP00000419465.1	Q9GZV5
WWTR1	ENST00000884351.1		c.-107-3C>T	splice_region intron	N/A	ENSP00000554410.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over