chr1-3690596-G-A

Variant names:

• chr1-3690596-G-A
• rs12121865
• NM_005427.4:c.186+7416G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005427.4(TP73):​c.186+7416G>A variant causes a intron change. The variant allele was found at a frequency of 0.0586 in 1,256,496 control chromosomes in the GnomAD database, including 2,437 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 0.040 (161 hom., cov: 33)
  • Exomes 𝑓: 0.061 (2276 hom.)
• Consequence: TP73 NM_005427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.07
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TP73	NM_005427.4	c.186+7416G>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+7416G>A		intron_variant	Intron 3 of 13	1	NM_005427.4	ENSP00000367545.4

Frequencies

GnomAD3 genomes AF: 0.0398 AC: 6055 AN: 152228 Hom.: 161 Cov.: 33

Gnomad AFR AF: 0.00991

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0402

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.0425

GnomAD4 exome AF: 0.0612 AC: 67560 AN: 1104150 Hom.: 2276 AF XY: 0.0602 AC XY: 31752 AN XY: 527706

African (AFR) AF: 0.00850 AC: 204 AN: 23994

American (AMR) AF: 0.0328 AC: 412 AN: 12578

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 555 AN: 13562

East Asian (EAS) AF: 0.0000477 AC: 1 AN: 20970

South Asian (SAS) AF: 0.0161 AC: 804 AN: 49856

European-Finnish (FIN) AF: 0.0399 AC: 660 AN: 16540

Middle Eastern (MID) AF: 0.0380 AC: 105 AN: 2762

European-Non Finnish (NFE) AF: 0.0677 AC: 62388 AN: 920888

Other (OTH) AF: 0.0565 AC: 2431 AN: 43000

GnomAD4 genome AF: 0.0397 AC: 6055 AN: 152346 Hom.: 161 Cov.: 33 AF XY: 0.0382 AC XY: 2847 AN XY: 74490

African (AFR) AF: 0.00988 AC: 411 AN: 41596

American (AMR) AF: 0.0437 AC: 669 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0366 AC: 127 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4830

European-Finnish (FIN) AF: 0.0402 AC: 427 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0623 AC: 4238 AN: 68030

Other (OTH) AF: 0.0416 AC: 88 AN: 2116

Alfa AF: 0.0149 Hom.: 8

Bravo AF: 0.0397

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Benign	0.76
PhyloP100		7.1
PromoterAI		0.021	Neutral
Mutation Taster		=100/0	polymorphism

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: rs12121865; hg19: chr1-3607160;