rs11250080

Variant names:

• chr8-10816957-T-C
• rs11250080
• NM_017884.6:c.471+3236A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ENSG00000306912 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PINX1	NM_017884.6	c.471+3236A>G		intron_variant	Intron 6 of 6	ENST00000314787.8	NP_060354.4
PINX1	NM_001284356.2	c.394+9195A>G		intron_variant	Intron 5 of 5		NP_001271285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8	c.471+3236A>G		intron_variant	Intron 6 of 6	1	NM_017884.6	ENSP00000318966.3
PINX1	ENST00000554914.1	c.394+9195A>G		intron_variant	Intron 5 of 5	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

African (AFR) AF: 0.423 AC: 17525 AN: 41444

American (AMR) AF: 0.371 AC: 5677 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1310 AN: 3472

East Asian (EAS) AF: 0.351 AC: 1813 AN: 5172

South Asian (SAS) AF: 0.246 AC: 1186 AN: 4820

European-Finnish (FIN) AF: 0.275 AC: 2900 AN: 10550

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21100 AN: 67978

Other (OTH) AF: 0.358 AC: 757 AN: 2114

Alfa AF: 0.329 Hom.: 16270

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
PhyloP100		0.047
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: rs11250080; hg19: chr8-10674467;