dbSNP rs1181868: TP73:c.*1483G>T (chr1-3734562-G-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.*1483G>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 152,180 control chromosomes in the GnomAD database, including 26,302 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 ( 26263 hom., cov: 32)

Exomes 𝑓: 0.78 ( 39 hom. )

Consequence

TP73
NM_005427.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0120

Publications

7 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=-0.84).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP73	NM_005427.4 link	c.*1483G>T		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.*1483G>T		3_prime_UTR_variant	Exon 14 of 14	1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes

AF:

0.539

AC:

81938

AN:

151934

Hom.:

26260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.756

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.717

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.735

Gnomad OTH

AF:

0.588

GnomAD4 exome

AF:

0.781

AC:

100

AN:

128

Hom.:

Cov.:

AF XY:

0.798

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.800

AC:

AN:

110

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

81948

AN:

152052

Hom.:

26263

Cov.:

AF XY:

0.533

AC XY:

39604

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.198

AC:

8230

AN:

41476

American (AMR)

AF:

0.565

AC:

8628

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.717

AC:

2490

AN:

3472

East Asian (EAS)

AF:

0.263

AC:

1355

AN:

5150

South Asian (SAS)

AF:

0.464

AC:

2232

AN:

4814

European-Finnish (FIN)

AF:

0.658

AC:

6972

AN:

10588

Middle Eastern (MID)

AF:

0.596

AC:

174

AN:

292

European-Non Finnish (NFE)

AF:

0.735

AC:

49943

AN:

67962

Other (OTH)

AF:

0.587

AC:

1236

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1567

3134

4701

6268

7835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.671

Hom.:

61513

Bravo

AF:

0.519

Asia WGS

AF:

0.364

AC:

1263

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

(source)

DANN

Benign

0.54

PhyloP100

-0.012

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over