rs910870

Positions:

• chr20-34705089-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021202.3(TP53INP2):​c.-166-269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,050 control chromosomes in the GnomAD database, including 20,194 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 0.49 (20194 hom., cov: 32)
• Consequence: TP53INP2 NM_021202.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

Genes affected

TP53INP2 (HGNC:16104): (tumor protein p53 inducible nuclear protein 2) The protein encoded by this gene promotes autophagy and is essential for proper autophagosome formation and processing. In addition, the encoded protein can enhance rDNA transcription by helping in the assembly of the POLR1/RNA polymerase I preinitiation complex. Finally, this protein serves as a transcriptional activator for some genes. [provided by RefSeq, Jul 2016]

NCOA6 (HGNC:15936): (nuclear receptor coactivator 6) The protein encoded by this gene is a transcriptional coactivator that can interact with nuclear hormone receptors to enhance their transcriptional activator functions. This protein has been shown to be involved in the hormone-dependent coactivation of several receptors, including prostanoid, retinoid, vitamin D3, thyroid hormone, and steroid receptors. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TP53INP2	NM_021202.3	c.-166-269T>C		intron_variant		ENST00000374810.8
TP53INP2	NM_001329429.2	c.-148-269T>C		intron_variant
TP53INP2	NM_001329430.2	c.-50+577T>C		intron_variant
TP53INP2	NM_001329431.2	c.-166-269T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TP53INP2	ENST00000374810.8	c.-166-269T>C		intron_variant		1	NM_021202.3	P1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73886 AN: 151932 Hom.: 20153 Cov.: 32

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.486 AC: 73972 AN: 152050 Hom.: 20194 Cov.: 32 AF XY: 0.483 AC XY: 35884 AN XY: 74326

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.456

Alfa AF: 0.420 Hom.: 2695

Bravo AF: 0.488

Asia WGS AF: 0.338 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.0
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs910870; hg19: chr20-33292893;