1-3734845-G-A

Variant names:

• chr1-3734845-G-A
• rs10910018
• NM_005427.4:c.*1766G>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.*1766G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 151,890 control chromosomes in the GnomAD database, including 238 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 0.036 (238 hom., cov: 33)
  • Exomes 𝑓: 0.030 (0 hom.)
• Consequence: TP73 NM_005427.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 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.*1766G>A		3_prime_UTR	Exon 14 of 14	NP_005418.1
	TP73	NM_001126240.3		c.*1766G>A		3_prime_UTR	Exon 12 of 12	NP_001119712.1
	TP73	NM_001204192.2		c.*1766G>A		3_prime_UTR	Exon 12 of 12	NP_001191121.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TP73	ENST00000378295.9	TSL:1 MANE Select	c.*1766G>A		3_prime_UTR	Exon 14 of 14	ENSP00000367545.4
	TP73	ENST00000378288.8	TSL:1	c.*1766G>A		3_prime_UTR	Exon 12 of 12	ENSP00000367537.4
	TP73	ENST00000713570.1		c.*1766G>A		3_prime_UTR	Exon 14 of 14	ENSP00000518863.1

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5435 AN: 151606 Hom.: 239 Cov.: 33

Gnomad AFR AF: 0.00817

Gnomad AMI AF: 0.0925

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.0296

Gnomad FIN AF: 0.0512

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.0312

GnomAD4 exome AF: 0.0298 AC: 5 AN: 168 Hom.: 0 Cov.: 0 AF XY: 0.0385 AC XY: 5 AN XY: 130

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.214 AC: 3 AN: 14

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0169 AC: 2 AN: 118

Other (OTH) AF: 0.00 AC: 0 AN: 14

GnomAD4 genome AF: 0.0358 AC: 5429 AN: 151722 Hom.: 238 Cov.: 33 AF XY: 0.0369 AC XY: 2740 AN XY: 74200

African (AFR) AF: 0.00814 AC: 334 AN: 41022

American (AMR) AF: 0.0194 AC: 297 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3472

East Asian (EAS) AF: 0.220 AC: 1135 AN: 5150

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4834

European-Finnish (FIN) AF: 0.0512 AC: 544 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0389 AC: 2649 AN: 68018

Other (OTH) AF: 0.0318 AC: 67 AN: 2110

Alfa AF: 0.0387 Hom.: 45

Bravo AF: 0.0340

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.57
PhyloP100		0.23
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: rs10910018; hg19: chr1-3651409;