rs3730814

Variant names:

• chr18-54292531-G-T
• rs2718886
• NM_007195.3:c.1404+493G>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.1404+493G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,984 control chromosomes in the GnomAD database, including 2,660 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 (2660 hom., cov: 32)
• Consequence: POLI NM_007195.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 0 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.1404+493G>T		intron_variant	Intron 9 of 9	ENST00000579534.6	NP_009126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLI	ENST00000579534.6	c.1404+493G>T		intron_variant	Intron 9 of 9	1	NM_007195.3	ENSP00000462664.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27292 AN: 151866 Hom.: 2661 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.259

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: 0.180 AC: 27283 AN: 151984 Hom.: 2660 Cov.: 32 AF XY: 0.175 AC XY: 13011 AN XY: 74282

African (AFR) AF: 0.136 AC: 5633 AN: 41490

American (AMR) AF: 0.168 AC: 2565 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 810 AN: 3464

East Asian (EAS) AF: 0.0232 AC: 120 AN: 5176

South Asian (SAS) AF: 0.190 AC: 917 AN: 4824

European-Finnish (FIN) AF: 0.153 AC: 1617 AN: 10570

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15092 AN: 67888

Other (OTH) AF: 0.181 AC: 382 AN: 2106

Alfa AF: 0.201 Hom.: 1613

Bravo AF: 0.176

Asia WGS AF: 0.0980 AC: 340 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.5
DANN	Benign	0.66
PhyloP100		-0.23
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: rs2718886; hg19: chr18-51818901;