rs3730729

Variant names:

• chr18-54278332-C-T
• rs3730729
• NM_007195.3:c.559+477C>T

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+477C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,078 control chromosomes in the GnomAD database, including 2,702 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 0.18 (2702 hom., cov: 32)
• Consequence: POLI NM_007195.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLI	NM_007195.3	c.559+477C>T		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+477C>T		intron_variant	Intron 4 of 9	1	NM_007195.3	ENSP00000462664.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27645 AN: 151960 Hom.: 2703 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.182 AC: 27635 AN: 152078 Hom.: 2702 Cov.: 32 AF XY: 0.177 AC XY: 13188 AN XY: 74342

African (AFR) AF: 0.144 AC: 5953 AN: 41482

American (AMR) AF: 0.168 AC: 2574 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3468

East Asian (EAS) AF: 0.0231 AC: 120 AN: 5186

South Asian (SAS) AF: 0.190 AC: 914 AN: 4814

European-Finnish (FIN) AF: 0.153 AC: 1619 AN: 10582

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.222 AC: 15116 AN: 67950

Other (OTH) AF: 0.181 AC: 383 AN: 2112

Alfa AF: 0.213 Hom.: 1999

Bravo AF: 0.179

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.48
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3730729; hg19: chr18-51804702;