chr1-3675623-C-T

Variant names:

• chr1-3675623-C-T
• rs3765702
• NM_005427.4:c.-33-6710C>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.-33-6710C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,808 control chromosomes in the GnomAD database, including 15,166 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 0.44 (15166 hom., cov: 31)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• 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: ClinGen, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP73	NM_005427.4	c.-33-6710C>T		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.-33-6710C>T		intron_variant	Intron 1 of 13	1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66785 AN: 151690 Hom.: 15130 Cov.: 31

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.441 AC: 66880 AN: 151808 Hom.: 15166 Cov.: 31 AF XY: 0.448 AC XY: 33267 AN XY: 74190

African (AFR) AF: 0.534 AC: 22116 AN: 41408

American (AMR) AF: 0.476 AC: 7270 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1068 AN: 3470

East Asian (EAS) AF: 0.455 AC: 2315 AN: 5088

South Asian (SAS) AF: 0.519 AC: 2487 AN: 4796

European-Finnish (FIN) AF: 0.505 AC: 5325 AN: 10554

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.369 AC: 25034 AN: 67896

Other (OTH) AF: 0.409 AC: 864 AN: 2114

Alfa AF: 0.386 Hom.: 16644

Bravo AF: 0.440

Asia WGS AF: 0.516 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.29
PhyloP100		-1.9
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: rs3765702; hg19: chr1-3592187;