rs596986

Positions:

• chr18-54295130-G-C

Variant summary

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

The NM_007195.3(POLI):​c.*663G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 985,216 control chromosomes in the GnomAD database, including 2,057 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 0.066 (387 hom., cov: 32)
  • Exomes 𝑓: 0.063 (1670 hom.)
• Consequence: POLI NM_007195.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLI	NM_007195.3	c.*663G>C		3_prime_UTR_variant	10/10	ENST00000579534.6	NP_009126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLI	ENST00000579534.6	c.*663G>C		3_prime_UTR_variant	10/10	1	NM_007195.3	ENSP00000462664.1
POLI	ENST00000579823.1	c.331+7719G>C		intron_variant		3		ENSP00000463065.1

Frequencies

GnomAD3 genomes AF: 0.0660 AC: 10037 AN: 152056 Hom.: 385 Cov.: 32

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0685

Gnomad EAS AF: 0.00482

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0684

Gnomad OTH AF: 0.0717

GnomAD4 exome AF: 0.0625 AC: 52083 AN: 833042 Hom.: 1670 Cov.: 30 AF XY: 0.0628 AC XY: 24159 AN XY: 384680

Gnomad4 AFR exome AF: 0.0798

Gnomad4 AMR exome AF: 0.0346

Gnomad4 ASJ exome AF: 0.0718

Gnomad4 EAS exome AF: 0.00193

Gnomad4 SAS exome AF: 0.0286

Gnomad4 FIN exome AF: 0.0471

Gnomad4 NFE exome AF: 0.0634

Gnomad4 OTH exome AF: 0.0566

GnomAD4 genome AF: 0.0660 AC: 10043 AN: 152174 Hom.: 387 Cov.: 32 AF XY: 0.0658 AC XY: 4897 AN XY: 74410

Gnomad4 AFR AF: 0.0773

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.0685

Gnomad4 EAS AF: 0.00483

Gnomad4 SAS AF: 0.0282

Gnomad4 FIN AF: 0.0679

Gnomad4 NFE AF: 0.0684

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0670 Hom.: 56

Bravo AF: 0.0664

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.1
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: rs596986; hg19: chr18-51821500;