NM_005427.4:c.1578+225G>A

Variant names:

• chr1-3731781-G-A
• rs6695978
• NM_005427.4:c.1578+225G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005427.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP73	NM_005427.4	MANE Select	c.1578+225G>A		intron	N/A	NP_005418.1
	TP73	NM_001126240.3		c.1431+225G>A		intron	N/A	NP_001119712.1
	TP73	NM_001204192.2		c.1365+225G>A		intron	N/A	NP_001191121.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP73	ENST00000378295.9	TSL:1 MANE Select	c.1578+225G>A		intron	N/A	ENSP00000367545.4
	TP73	ENST00000378288.8	TSL:1	c.1431+225G>A		intron	N/A	ENSP00000367537.4
	TP73	ENST00000378285.5	TSL:1	c.1337+716G>A		intron	N/A	ENSP00000367534.1

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

African (AFR) AF: 0.133 AC: 5525 AN: 41562

American (AMR) AF: 0.0376 AC: 576 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1147 AN: 5176

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4822

European-Finnish (FIN) AF: 0.0515 AC: 547 AN: 10626

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0399 AC: 2716 AN: 68024

Other (OTH) AF: 0.0572 AC: 121 AN: 2116

Alfa AF: 0.0496 Hom.: 371

Bravo AF: 0.0758

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.73
DANN	Benign	0.61
PhyloP100		-2.4
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: rs6695978; hg19: chr1-3648345;