rs7826180

Positions:

• chr8-10770334-G-A
• chr8-10770334-G-C

Variant summary

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

The NM_017884.6(PINX1):​c.472-4418C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,206 control chromosomes in the GnomAD database, including 4,232 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 0.23 (4232 hom., cov: 33)
• Consequence: PINX1 NM_017884.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

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]

ENSG00000248896 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PINX1	NM_017884.6	c.472-4418C>T		intron_variant		ENST00000314787.8	NP_060354.4
PINX1	NM_001284356.2	c.395-4418C>T		intron_variant			NP_001271285.1
LOC102723313	NR_146188.1	n.402-182G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PINX1	ENST00000314787.8	c.472-4418C>T		intron_variant		1	NM_017884.6	ENSP00000318966.3
PINX1	ENST00000554914.1	c.395-43668C>T		intron_variant		2		ENSP00000451145.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35433 AN: 152088 Hom.: 4225 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.233 AC: 35461 AN: 152206 Hom.: 4232 Cov.: 33 AF XY: 0.233 AC XY: 17328 AN XY: 74398

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.253

Alfa AF: 0.230 Hom.: 7036

Bravo AF: 0.239

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.71

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: rs7826180; hg19: chr8-10627844;