chr1-3734562-G-T

Variant names:

• chr1-3734562-G-T
• rs1181868
• NM_005427.4:c.*1483G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005427.4(TP73):​c.*1483G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,180 control chromosomes in the GnomAD database, including 26,302 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 0.54 (26263 hom., cov: 32)
  • Exomes 𝑓: 0.78 (39 hom.)
• Consequence: TP73 NM_005427.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 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.*1483G>T		3_prime_UTR	Exon 14 of 14	NP_005418.1
	TP73	NM_001126240.3		c.*1483G>T		3_prime_UTR	Exon 12 of 12	NP_001119712.1
	TP73	NM_001204192.2		c.*1483G>T		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.*1483G>T		3_prime_UTR	Exon 14 of 14	ENSP00000367545.4
	TP73	ENST00000378288.8	TSL:1	c.*1483G>T		3_prime_UTR	Exon 12 of 12	ENSP00000367537.4
	TP73	ENST00000713570.1		c.*1483G>T		3_prime_UTR	Exon 14 of 14	ENSP00000518863.1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81938 AN: 151934 Hom.: 26260 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.781 AC: 100 AN: 128 Hom.: 39 Cov.: 0 AF XY: 0.798 AC XY: 67 AN XY: 84

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.800 AC: 88 AN: 110

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.539 AC: 81948 AN: 152052 Hom.: 26263 Cov.: 32 AF XY: 0.533 AC XY: 39604 AN XY: 74328

African (AFR) AF: 0.198 AC: 8230 AN: 41476

American (AMR) AF: 0.565 AC: 8628 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2490 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1355 AN: 5150

South Asian (SAS) AF: 0.464 AC: 2232 AN: 4814

European-Finnish (FIN) AF: 0.658 AC: 6972 AN: 10588

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.735 AC: 49943 AN: 67962

Other (OTH) AF: 0.587 AC: 1236 AN: 2104

Alfa AF: 0.671 Hom.: 61513

Bravo AF: 0.519

Asia WGS AF: 0.364 AC: 1263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.54
PhyloP100		-0.012
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: rs1181868; hg19: chr1-3651126;