1-3682336-G-A

Variant names:

• chr1-3682336-G-A
• rs2273953
• NM_005427.4:c.-30G>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.-30G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,494,602 control chromosomes in the GnomAD database, including 32,109 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 0.19 (2816 hom., cov: 34)
  • Exomes 𝑓: 0.21 (29293 hom.)
• Consequence: TP73 NM_005427.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399
• Publications: 39 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.268 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.-30G>A		5_prime_UTR	Exon 2 of 14	NP_005418.1
	TP73	NM_001204187.2		c.-30G>A		5_prime_UTR	Exon 2 of 12	NP_001191116.1
	TP73	NM_001204188.2		c.-30G>A		5_prime_UTR	Exon 2 of 12	NP_001191117.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP73	ENST00000378295.9	TSL:1 MANE Select	c.-30G>A		5_prime_UTR	Exon 2 of 14	ENSP00000367545.4
	TP73	ENST00000713571.1		n.83G>A		non_coding_transcript_exon	Exon 2 of 5
	TP73	ENST00000713570.1		c.-30G>A		5_prime_UTR	Exon 2 of 14	ENSP00000518863.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28373 AN: 152084 Hom.: 2813 Cov.: 34

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.196

GnomAD2 exomes AF: 0.203 AC: 27759 AN: 136584 AF XY: 0.198

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.279

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.227

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.206 AC: 276765 AN: 1342398 Hom.: 29293 Cov.: 31 AF XY: 0.204 AC XY: 134375 AN XY: 658662

African (AFR) AF: 0.123 AC: 3706 AN: 30068

American (AMR) AF: 0.283 AC: 9130 AN: 32308

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 4565 AN: 22594

East Asian (EAS) AF: 0.239 AC: 8086 AN: 33776

South Asian (SAS) AF: 0.137 AC: 10030 AN: 73232

European-Finnish (FIN) AF: 0.180 AC: 8501 AN: 47254

Middle Eastern (MID) AF: 0.197 AC: 1065 AN: 5412

European-Non Finnish (NFE) AF: 0.211 AC: 220402 AN: 1042866

Other (OTH) AF: 0.206 AC: 11280 AN: 54888

GnomAD4 genome AF: 0.187 AC: 28394 AN: 152204 Hom.: 2816 Cov.: 34 AF XY: 0.188 AC XY: 13982 AN XY: 74410

African (AFR) AF: 0.128 AC: 5327 AN: 41546

American (AMR) AF: 0.275 AC: 4209 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 689 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1119 AN: 5158

South Asian (SAS) AF: 0.140 AC: 677 AN: 4832

European-Finnish (FIN) AF: 0.187 AC: 1984 AN: 10592

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13831 AN: 67988

Other (OTH) AF: 0.194 AC: 411 AN: 2114

Alfa AF: 0.122 Hom.: 286

Bravo AF: 0.193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.1
DANN	Benign	0.74
PhyloP100		0.40
PromoterAI		-0.012	Neutral
Mutation Taster		=299/1	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: rs2273953; hg19: chr1-3598900; COSMIC: COSV60702093; COSMIC: COSV60702093;