rs545979

Variant names:

• chr18-54293380-C-T
• rs545979
• NM_007195.3:c.1405-269C>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.1405-269C>T 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 151,700 control chromosomes in the GnomAD database, including 5,083 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 (5083 hom., cov: 31)
• Consequence: POLI NM_007195.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.940
• Publications: 27 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007195.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLI	NM_007195.3	MANE Select	c.1405-269C>T		intron	N/A	NP_009126.2	Q9UNA4
	POLI	NM_001351632.2		c.1330-269C>T		intron	N/A	NP_001338561.1
	POLI	NM_001351610.1		c.1279-269C>T		intron	N/A	NP_001338539.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLI	ENST00000579534.6	TSL:1 MANE Select	c.1405-269C>T		intron	N/A	ENSP00000462664.1	Q9UNA4
	POLI	ENST00000579434.5	TSL:1	c.1096-269C>T		intron	N/A	ENSP00000462681.1	J3KSW2
	POLI	ENST00000585023.5	TSL:1	n.*500-269C>T		intron	N/A	ENSP00000463971.1	J3QQZ8

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38434 AN: 151584 Hom.: 5084 Cov.: 31

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.0297

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.222

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: 38441 AN: 151700 Hom.: 5083 Cov.: 31 AF XY: 0.249 AC XY: 18461 AN XY: 74094

African (AFR) AF: 0.236 AC: 9762 AN: 41366

American (AMR) AF: 0.222 AC: 3387 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3468

East Asian (EAS) AF: 0.0296 AC: 153 AN: 5174

South Asian (SAS) AF: 0.248 AC: 1193 AN: 4820

European-Finnish (FIN) AF: 0.222 AC: 2330 AN: 10496

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19753 AN: 67822

Other (OTH) AF: 0.259 AC: 545 AN: 2108

Alfa AF: 0.283 Hom.: 3668

Bravo AF: 0.251

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.66
PhyloP100		0.94
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: rs545979; hg19: chr18-51819750;