rs11250080

Positions:

• chr8-10816957-T-C

Variant summary

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

The NM_017884.6(PINX1):​c.471+3236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,046 control chromosomes in the GnomAD database, including 9,338 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 0.35 (9338 hom., cov: 32)
• Consequence: PINX1 NM_017884.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

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 (AFR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PINX1	NM_017884.6	c.471+3236A>G		intron_variant		ENST00000314787.8	NP_060354.4
PINX1	NM_001284356.2	c.394+9195A>G		intron_variant			NP_001271285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8	c.471+3236A>G		intron_variant		1	NM_017884.6	ENSP00000318966.3
PINX1	ENST00000554914.1	c.394+9195A>G		intron_variant		2		ENSP00000451145.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52437 AN: 151928 Hom.: 9321 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.345 AC: 52495 AN: 152046 Hom.: 9338 Cov.: 32 AF XY: 0.342 AC XY: 25422 AN XY: 74322

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.358

Alfa AF: 0.321 Hom.: 11418

Bravo AF: 0.356

Asia WGS AF: 0.287 AC: 997 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	1.5
DANN	Benign	0.40

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: rs11250080; hg19: chr8-10674467;