18-54295130-G-C

Variant names:

• chr18-54295130-G-C
• rs596986
• NM_007195.3:c.*663G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.85).
• 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 rank	MANE	Protein	UniProt
POLI	NM_007195.3	c.*663G>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000579534.6	NP_009126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLI	ENST00000579534.6	c.*663G>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_007195.3	ENSP00000462664.1
POLI	ENST00000579823.1	c.331+7719G>C		intron_variant	Intron 3 of 4	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

African (AFR) AF: 0.0798 AC: 1260 AN: 15788

American (AMR) AF: 0.0346 AC: 34 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0718 AC: 370 AN: 5152

East Asian (EAS) AF: 0.00193 AC: 7 AN: 3632

South Asian (SAS) AF: 0.0286 AC: 470 AN: 16454

European-Finnish (FIN) AF: 0.0471 AC: 13 AN: 276

Middle Eastern (MID) AF: 0.0408 AC: 66 AN: 1618

European-Non Finnish (NFE) AF: 0.0634 AC: 48318 AN: 761842

Other (OTH) AF: 0.0566 AC: 1545 AN: 27296

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

African (AFR) AF: 0.0773 AC: 3210 AN: 41530

American (AMR) AF: 0.0513 AC: 783 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0685 AC: 238 AN: 3472

East Asian (EAS) AF: 0.00483 AC: 25 AN: 5178

South Asian (SAS) AF: 0.0282 AC: 136 AN: 4822

European-Finnish (FIN) AF: 0.0679 AC: 720 AN: 10608

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0684 AC: 4651 AN: 67974

Other (OTH) AF: 0.0724 AC: 153 AN: 2114

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
PhyloP100		-0.43
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: rs596986; hg19: chr18-51821500;