rs4648551

Variant names:

• chr1-3716166-G-A
• rs4648551
• NM_005427.4:c.430-5855G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005427.4(TP73):​c.430-5855G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,134 control chromosomes in the GnomAD database, including 9,681 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 0.32 (9681 hom., cov: 33)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP73	NM_005427.4	c.430-5855G>A		intron_variant	Intron 4 of 13	ENST00000378295.9	NP_005418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP73	ENST00000378295.9	c.430-5855G>A		intron_variant	Intron 4 of 13	1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48948 AN: 152016 Hom.: 9677 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.365

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.322 AC: 48954 AN: 152134 Hom.: 9681 Cov.: 33 AF XY: 0.323 AC XY: 23994 AN XY: 74368

African (AFR) AF: 0.116 AC: 4826 AN: 41526

American (AMR) AF: 0.378 AC: 5779 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1674 AN: 3470

East Asian (EAS) AF: 0.0143 AC: 74 AN: 5170

South Asian (SAS) AF: 0.297 AC: 1434 AN: 4822

European-Finnish (FIN) AF: 0.459 AC: 4855 AN: 10574

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29013 AN: 67966

Other (OTH) AF: 0.360 AC: 761 AN: 2112

Alfa AF: 0.376 Hom.: 1463

Bravo AF: 0.306

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.010
DANN	Benign	0.36
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4648551; hg19: chr1-3632730;