chr1-3690286-G-A

Variant names:

• chr1-3690286-G-A
• rs3765728
• NM_005427.4:c.186+7106G>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.186+7106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,998 control chromosomes in the GnomAD database, including 37,316 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 0.69 (37316 hom., cov: 33)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.452
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP73	NM_005427.4	c.186+7106G>A		intron_variant	Intron 3 of 13	ENST00000378295.9	NP_005418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TP73	ENST00000378295.9	c.186+7106G>A		intron_variant	Intron 3 of 13	1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104724 AN: 151880 Hom.: 37315 Cov.: 33

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.695

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.689 AC: 104748 AN: 151998 Hom.: 37316 Cov.: 33 AF XY: 0.684 AC XY: 50824 AN XY: 74316

African (AFR) AF: 0.530 AC: 21968 AN: 41446

American (AMR) AF: 0.588 AC: 8995 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2719 AN: 3468

East Asian (EAS) AF: 0.555 AC: 2847 AN: 5132

South Asian (SAS) AF: 0.689 AC: 3314 AN: 4810

European-Finnish (FIN) AF: 0.746 AC: 7920 AN: 10616

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54469 AN: 67924

Other (OTH) AF: 0.700 AC: 1478 AN: 2110

Alfa AF: 0.716 Hom.: 3603

Bravo AF: 0.669

Asia WGS AF: 0.597 AC: 2077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.47
PhyloP100		0.45
PromoterAI		-0.0098	Neutral
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: rs3765728; hg19: chr1-3606850;