rs2409655

chr8-10818322-A-G

Variant summary

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

The NM_017884.6(PINX1):c.471+1871T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,114 control chromosomes in the GnomAD database, including 5,260 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 0.26 (5260 hom., cov: 31)
• Consequence: PINX1 NM_017884.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688

Genes affected

PINX1 (HGNC:30046): (PIN2 (TERF1) interacting telomerase inhibitor 1) Enables telomerase RNA binding activity and telomerase inhibitor activity. Involved in several processes, including negative regulation of DNA biosynthetic process; positive regulation of protein localization to nucleolus; and protein localization to organelle. Acts upstream of or within telomere maintenance via telomerase. Located in several cellular components, including chromosomal region; nuclear lumen; and spindle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PINX1	NM_017884.6	c.471+1871T>C		intron_variant		ENST00000314787.8
PINX1	NM_001284356.2	c.394+7830T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PINX1	ENST00000314787.8	c.471+1871T>C		intron_variant		1	NM_017884.6	P2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38846 AN: 151996 Hom.: 5251 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.256 AC: 38878 AN: 152114 Hom.: 5260 Cov.: 31 AF XY: 0.252 AC XY: 18735 AN XY: 74362

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.00368

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.244

Alfa AF: 0.273 Hom.: 5089

Bravo AF: 0.247

Asia WGS AF: 0.142 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.56
Dann	Benign	0.53

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: rs2409655; hg19: chr8-10675832;