1-3667128-G-C

Variant names:

• chr1-3667128-G-C
• rs1885859
• NM_005427.4:c.-34+14487G>C

Variant summary

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

The NM_005427.4(TP73):​c.-34+14487G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 152,028 control chromosomes in the GnomAD database, including 38,164 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 0.70 (38164 hom., cov: 31)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996
• Publications: 6 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-AS3 (HGNC:40590): (TP73 antisense RNA 3)

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 (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP73	NM_005427.4	c.-34+14487G>C		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.-34+14487G>C		intron_variant	Intron 1 of 13	1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106024 AN: 151910 Hom.: 38128 Cov.: 31

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.698 AC: 106115 AN: 152028 Hom.: 38164 Cov.: 31 AF XY: 0.693 AC XY: 51487 AN XY: 74302

African (AFR) AF: 0.882 AC: 36598 AN: 41484

American (AMR) AF: 0.574 AC: 8770 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2402 AN: 3472

East Asian (EAS) AF: 0.650 AC: 3344 AN: 5144

South Asian (SAS) AF: 0.601 AC: 2890 AN: 4806

European-Finnish (FIN) AF: 0.610 AC: 6443 AN: 10568

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43369 AN: 67966

Other (OTH) AF: 0.698 AC: 1468 AN: 2104

Alfa AF: 0.564 Hom.: 1519

Bravo AF: 0.707

Asia WGS AF: 0.626 AC: 2178 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	0.43
DANN	Benign	0.22
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: rs1885859; hg19: chr1-3583692;