1-3700037-C-T

Variant names:

• chr1-3700037-C-T
• rs3765736
• NM_005427.4:c.187-7512C>T

Variant summary

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

The NM_005427.4(TP73):​c.187-7512C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,644 control chromosomes in the GnomAD database, including 8,802 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 0.33 (8802 hom., cov: 30)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• Publications: 10 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP73	NM_005427.4	c.187-7512C>T		intron_variant	Intron 3 of 13	ENST00000378295.9	NP_005418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP73	ENST00000378295.9	c.187-7512C>T		intron_variant	Intron 3 of 13	1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes AF: 0.330 AC: 49979 AN: 151528 Hom.: 8789 Cov.: 30

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.330 AC: 50029 AN: 151644 Hom.: 8802 Cov.: 30 AF XY: 0.332 AC XY: 24573 AN XY: 74088

African (AFR) AF: 0.230 AC: 9540 AN: 41420

American (AMR) AF: 0.283 AC: 4322 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1037 AN: 3462

East Asian (EAS) AF: 0.369 AC: 1880 AN: 5092

South Asian (SAS) AF: 0.276 AC: 1327 AN: 4806

European-Finnish (FIN) AF: 0.460 AC: 4831 AN: 10512

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.382 AC: 25919 AN: 67790

Other (OTH) AF: 0.317 AC: 669 AN: 2110

Alfa AF: 0.358 Hom.: 37539

Bravo AF: 0.315

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.61
PhyloP100		-0.14
Mutation Taster		=99/1	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: rs3765736; hg19: chr1-3616601; COSMIC: COSV60699140;