rs602422

Variant names:

• chr18-54278760-A-G
• rs602422
• NM_007195.3:c.559+905A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
POLI	NM_007195.3	c.559+905A>G		intron_variant	Intron 4 of 9	ENST00000579534.6	NP_009126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLI	ENST00000579534.6	c.559+905A>G		intron_variant	Intron 4 of 9	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

African (AFR) AF: 0.236 AC: 9797 AN: 41518

American (AMR) AF: 0.222 AC: 3399 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1048 AN: 3472

East Asian (EAS) AF: 0.0294 AC: 153 AN: 5196

South Asian (SAS) AF: 0.247 AC: 1194 AN: 4830

European-Finnish (FIN) AF: 0.221 AC: 2338 AN: 10602

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19793 AN: 67998

Other (OTH) AF: 0.259 AC: 547 AN: 2114

Alfa AF: 0.278 Hom.: 11863

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
PhyloP100		-0.10
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: rs602422; hg19: chr18-51805130;