rs602422

Positions:

• chr18-54278760-A-G

Variant summary

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

The NM_007195.3(POLI):​c.559+905A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,224 control chromosomes in the GnomAD database, including 5,101 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 0.25 (5101 hom., cov: 32)
• Consequence: POLI NM_007195.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

Genes affected

POLI (HGNC:9182): (DNA polymerase iota) The protein encoded by this gene is an error-prone DNA polymerase involved in DNA repair. The encoded protein promotes DNA synthesis across lesions in the template DNA, which other polymerases cannot do. The encoded polymerase inserts deoxynucleotides across lesions and then relies on DNA polymerase zeta to extend the nascent DNA strand to bypass the lesion. [provided by RefSeq, May 2017]

POLI (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLI	NM_007195.3	c.559+905A>G		intron_variant		ENST00000579534.6	NP_009126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLI	ENST00000579534.6	c.559+905A>G		intron_variant		1	NM_007195.3	ENSP00000462664.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38536 AN: 152106 Hom.: 5102 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.0296

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.253 AC: 38543 AN: 152224 Hom.: 5101 Cov.: 32 AF XY: 0.249 AC XY: 18521 AN XY: 74428

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.0294

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.259

Alfa AF: 0.284 Hom.: 8230

Bravo AF: 0.251

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.67

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: rs602422; hg19: chr18-51805130;