1-3690286-G-A

Position:

• chr1-3690286-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005427.4(TP73):​c.186+7106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,998 control chromosomes in the GnomAD database, including 37,316 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 0.69 (37316 hom., cov: 33)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP73	NM_005427.4	c.186+7106G>A		intron_variant		ENST00000378295.9	NP_005418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TP73	ENST00000378295.9	c.186+7106G>A		intron_variant		1	NM_005427.4	ENSP00000367545	P1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104724 AN: 151880 Hom.: 37315 Cov.: 33

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.689 AC: 104748 AN: 151998 Hom.: 37316 Cov.: 33 AF XY: 0.684 AC XY: 50824 AN XY: 74316

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.700

Alfa AF: 0.716 Hom.: 3603

Bravo AF: 0.669

Asia WGS AF: 0.597 AC: 2077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs3765728; hg19: chr1-3606850;