dbSNP rs10910018: TP73:c.*1766G>A (chr1-3734845-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_005427.4(TP73):c.*1766G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 151,890 control chromosomes in the GnomAD database, including 238 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 0.036 ( 238 hom., cov: 33)

Exomes 𝑓: 0.030 ( 0 hom. )

Consequence

TP73
NM_005427.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.226

Publications

9 publications found

Variant links:

Genes affected

TP73 (HGNC:12003): (tumor protein p73) This gene encodes a member of the p53 family of transcription factors involved in cellular responses to stress and development. It maps to a region on chromosome 1p36 that is frequently deleted in neuroblastoma and other tumors, and thought to contain multiple tumor suppressor genes. The demonstration that this gene is monoallelically expressed (likely from the maternal allele), supports the notion that it is a candidate gene for neuroblastoma. Many transcript variants resulting from alternative splicing and/or use of alternate promoters have been found for this gene, but the biological validity and the full-length nature of some variants have not been determined. [provided by RefSeq, Feb 2011]

TP73 Gene-Disease associations (from GenCC):

ciliary dyskinesia, primary, 47, and lissencephaly
Inheritance: AR Classification: STRONG Submitted by: ClinGen, G2P

TP73 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP73	NM_005427.4 link	c.*1766G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000378295.9	NP_005418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP73	ENST00000378295.9 link	c.*1766G>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes

AF:

0.0358

AC:

5435

AN:

151606

Hom.:

239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00817

Gnomad AMI

AF:

0.0925

Gnomad AMR

AF:

0.0194

Gnomad ASJ

AF:

0.0487

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.0512

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0389

Gnomad OTH

AF:

0.0312

GnomAD4 exome

AF:

0.0298

AC:

AN:

168

Hom.:

Cov.:

AF XY:

0.0385

AC XY:

AN XY:

130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.214

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0169

AC:

AN:

118

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0358

AC:

5429

AN:

151722

Hom.:

238

Cov.:

AF XY:

0.0369

AC XY:

2740

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.00814

AC:

334

AN:

41022

American (AMR)

AF:

0.0194

AC:

297

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0487

AC:

169

AN:

3472

East Asian (EAS)

AF:

0.220

AC:

1135

AN:

5150

South Asian (SAS)

AF:

0.0290

AC:

140

AN:

4834

European-Finnish (FIN)

AF:

0.0512

AC:

544

AN:

10618

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0389

AC:

2649

AN:

68018

Other (OTH)

AF:

0.0318

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

234

468

702

936

1170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0387

Hom.:

Bravo

AF:

0.0340

Asia WGS

AF:

0.0970

AC:

336

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.9

(source)

DANN

Benign

0.57

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over