dbSNP rs1181869: TP73:c.*1455C>T (chr1-3734534-C-T) – 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.*1455C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,078 control chromosomes in the GnomAD database, including 26,253 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 0.54 ( 26235 hom., cov: 32)

Exomes 𝑓: 0.74 ( 18 hom. )

Consequence

TP73
NM_005427.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.03

Publications

5 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: G2P, PanelApp Australia, ClinGen

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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005427.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TP73	NM_005427.4	MANE Select	c.*1455C>T	3_prime_UTR	Exon 14 of 14	NP_005418.1	O15350-1
TP73	NM_001126240.3		c.*1455C>T	3_prime_UTR	Exon 12 of 12	NP_001119712.1	O15350-8
TP73	NM_001204192.2		c.*1455C>T	3_prime_UTR	Exon 12 of 12	NP_001191121.1	O15350-11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TP73	ENST00000378295.9	TSL:1 MANE Select	c.*1455C>T	3_prime_UTR	Exon 14 of 14	ENSP00000367545.4	O15350-1
TP73	ENST00000378288.8	TSL:1	c.*1455C>T	3_prime_UTR	Exon 12 of 12	ENSP00000367537.4	O15350-8
TP73	ENST00000713570.1		c.*1455C>T	3_prime_UTR	Exon 14 of 14	ENSP00000518863.1	O15350-1

Frequencies

GnomAD3 genomes

AF:

0.539

AC:

81888

AN:

151892

Hom.:

26233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.754

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.717

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.659

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.735

Gnomad OTH

AF:

0.589

GnomAD4 exome

AF:

0.735

AC:

AN:

Hom.:

Cov.:

AF XY:

0.722

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)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.583

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.780

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.568

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.539

AC:

81897

AN:

152010

Hom.:

26235

Cov.:

AF XY:

0.532

AC XY:

39572

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.198

AC:

8227

AN:

41458

American (AMR)

AF:

0.565

AC:

8633

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.717

AC:

2488

AN:

3470

East Asian (EAS)

AF:

0.262

AC:

1349

AN:

5146

South Asian (SAS)

AF:

0.458

AC:

2200

AN:

4808

European-Finnish (FIN)

AF:

0.659

AC:

6975

AN:

10590

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.735

AC:

49921

AN:

67940

Other (OTH)

AF:

0.588

AC:

1240

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1537

3074

4612

6149

7686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.630

Hom.:

4101

Bravo

AF:

0.519

Asia WGS

AF:

0.360

AC:

1250

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.36

(source)

DANN

Benign

0.44

PhyloP100

-2.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over