rs2409655

Variant names:

• chr8-10818322-A-G
• rs2409655
• NM_017884.6:c.471+1871T>C

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+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
• Publications: 7 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]

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 (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017884.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINX1	NM_017884.6	MANE Select	c.471+1871T>C		intron	N/A	NP_060354.4
	PINX1	NM_001284356.2		c.394+7830T>C		intron	N/A	NP_001271285.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PINX1	ENST00000314787.8	TSL:1 MANE Select	c.471+1871T>C		intron	N/A	ENSP00000318966.3
	PINX1	ENST00000554914.1	TSL:2	c.394+7830T>C		intron	N/A	ENSP00000451145.1
	PINX1	ENST00000519088.5	TSL:1	c.394+7830T>C		intron	N/A	ENSP00000428853.1

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

African (AFR) AF: 0.263 AC: 10907 AN: 41490

American (AMR) AF: 0.189 AC: 2893 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3470

East Asian (EAS) AF: 0.00368 AC: 19 AN: 5170

South Asian (SAS) AF: 0.263 AC: 1264 AN: 4814

European-Finnish (FIN) AF: 0.247 AC: 2610 AN: 10586

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19146 AN: 67988

Other (OTH) AF: 0.244 AC: 514 AN: 2108

Alfa AF: 0.274 Hom.: 6978

Bravo AF: 0.247

Asia WGS AF: 0.142 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.56
DANN	Benign	0.53
PhyloP100		-0.69
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: rs2409655; hg19: chr8-10675832;