1-3682439-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_005427.4(TP73):c.65+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,508,870 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (8 hom.)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.376

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-3682439-G-A is Benign according to our data. Variant chr1-3682439-G-A is described in ClinVar as [Benign]. Clinvar id is 773386.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP73	NM_005427.4	c.65+9G>A		intron_variant		ENST00000378295.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP73	ENST00000378295.9	c.65+9G>A		intron_variant		1	NM_005427.4	P1

Frequencies

GnomAD3 genomes AF: 0.00183 AC: 279 AN: 152194 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00218

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00257 AC: 393 AN: 153186 Hom.: 0 AF XY: 0.00282 AC XY: 233 AN XY: 82530

Gnomad AFR exome AF: 0.000453

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.000133

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00411

Gnomad FIN exome AF: 0.00604

Gnomad NFE exome AF: 0.00251

Gnomad OTH exome AF: 0.00226

GnomAD4 exome AF: 0.00251 AC: 3399 AN: 1356558 Hom.: 8 Cov.: 31 AF XY: 0.00255 AC XY: 1694 AN XY: 665526

Gnomad4 AFR exome AF: 0.000457

Gnomad4 AMR exome AF: 0.00186

Gnomad4 ASJ exome AF: 0.000170

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00375

Gnomad4 FIN exome AF: 0.00528

Gnomad4 NFE exome AF: 0.00250

Gnomad4 OTH exome AF: 0.00263

GnomAD4 genome AF: 0.00183 AC: 279 AN: 152312 Hom.: 1 Cov.: 33 AF XY: 0.00188 AC XY: 140 AN XY: 74484

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00517

Gnomad4 FIN AF: 0.00612

Gnomad4 NFE AF: 0.00218

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00165 Hom.: 0

Bravo AF: 0.00150

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.6
Dann	Benign	0.48

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: rs141679680; hg19: chr1-3599003;