rs6695978

Positions:

• chr1-3731781-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.1578+225G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 152,308 control chromosomes in the GnomAD database, including 618 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 0.072 (618 hom., cov: 34)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TP73	NM_005427.4	c.1578+225G>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.1578+225G>A		intron_variant		1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 11021 AN: 152190 Hom.: 618 Cov.: 34

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0568

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

GnomAD4 genome AF: 0.0725 AC: 11041 AN: 152308 Hom.: 618 Cov.: 34 AF XY: 0.0728 AC XY: 5419 AN XY: 74472

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0376

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0399

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0595 Hom.: 82

Bravo AF: 0.0758

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.73
DANN	Benign	0.61

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: rs6695978; hg19: chr1-3648345;