rs3765703

Variant names:

• chr1-3675872-T-G
• rs3765703
• NM_005427.4:c.-33-6461T>G

Variant summary

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

The NM_005427.4(TP73):​c.-33-6461T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 151,880 control chromosomes in the GnomAD database, including 13,182 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 0.42 (13182 hom., cov: 31)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 11 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP73	NM_005427.4	c.-33-6461T>G		intron_variant	Intron 1 of 13	ENST00000378295.9	NP_005418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP73	ENST00000378295.9	c.-33-6461T>G		intron_variant	Intron 1 of 13	1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63033 AN: 151762 Hom.: 13173 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.415 AC: 63094 AN: 151880 Hom.: 13182 Cov.: 31 AF XY: 0.420 AC XY: 31150 AN XY: 74222

African (AFR) AF: 0.382 AC: 15841 AN: 41432

American (AMR) AF: 0.487 AC: 7444 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1643 AN: 3470

East Asian (EAS) AF: 0.311 AC: 1594 AN: 5122

South Asian (SAS) AF: 0.457 AC: 2198 AN: 4812

European-Finnish (FIN) AF: 0.440 AC: 4642 AN: 10556

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.418 AC: 28390 AN: 67890

Other (OTH) AF: 0.410 AC: 862 AN: 2104

Alfa AF: 0.422 Hom.: 50870

Bravo AF: 0.417

Asia WGS AF: 0.425 AC: 1474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.3
DANN	Benign	0.41
PhyloP100		-0.15
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: rs3765703; hg19: chr1-3592436;