rs3765701

Variant names:

• chr1-3672437-T-A
• rs3765701
• NM_005427.4:c.-33-9896T>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.-33-9896T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 151,856 control chromosomes in the GnomAD database, including 23,312 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 0.55 (23312 hom., cov: 32)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 7 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: G2P, PanelApp Australia, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.597 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP73	NM_005427.4	MANE Select	c.-33-9896T>A		intron	N/A	NP_005418.1	O15350-1
	TP73	NM_001204187.2		c.-33-9896T>A		intron	N/A	NP_001191116.1	O15350-13
	TP73	NM_001204188.2		c.-33-9896T>A		intron	N/A	NP_001191117.1	O15350-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP73	ENST00000378295.9	TSL:1 MANE Select	c.-33-9896T>A		intron	N/A	ENSP00000367545.4	O15350-1
	TP73	ENST00000713570.1		c.-34+3270T>A		intron	N/A	ENSP00000518863.1	O15350-1
	TP73	ENST00000603362.6	TSL:5	c.-33-9896T>A		intron	N/A	ENSP00000474626.1	O15350-13

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83234 AN: 151738 Hom.: 23295 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.548 AC: 83292 AN: 151856 Hom.: 23312 Cov.: 32 AF XY: 0.543 AC XY: 40279 AN XY: 74206

African (AFR) AF: 0.535 AC: 22132 AN: 41376

American (AMR) AF: 0.435 AC: 6647 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2381 AN: 3470

East Asian (EAS) AF: 0.526 AC: 2708 AN: 5152

South Asian (SAS) AF: 0.616 AC: 2968 AN: 4822

European-Finnish (FIN) AF: 0.444 AC: 4695 AN: 10576

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39792 AN: 67890

Other (OTH) AF: 0.596 AC: 1253 AN: 2102

Alfa AF: 0.476 Hom.: 1456

Bravo AF: 0.548

Asia WGS AF: 0.544 AC: 1897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.35
PhyloP100		-1.0
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: rs3765701; hg19: chr1-3589001;