18-54269477-G-T

Position:

• chr18-54269477-G-T

Variant summary

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

The ENST00000621167.1(ENSG00000277324):​n.552C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,480,554 control chromosomes in the GnomAD database, including 129,236 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 0.38 (11742 hom., cov: 33)
  • Exomes 𝑓: 0.42 (117494 hom.)
• Consequence: ENSG00000277324 ENST00000621167.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.834

Genes affected

ENSG00000277324 (HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLI	NM_007195.3	c.-70G>T		upstream_gene_variant		ENST00000579534.6	NP_009126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000277324	ENST00000621167.1	n.552C>A		non_coding_transcript_exon_variant	1/1	6
POLI	ENST00000579534.6	c.-70G>T		upstream_gene_variant		1	NM_007195.3	ENSP00000462664.1
POLI	ENST00000406285.7	c.-70G>T		upstream_gene_variant		2		ENSP00000385196.3

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57616 AN: 152008 Hom.: 11742 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.416 AC: 552557 AN: 1328428 Hom.: 117494 Cov.: 32 AF XY: 0.418 AC XY: 274053 AN XY: 655030

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.488

Gnomad4 EAS exome AF: 0.711

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.403

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.379 AC: 57627 AN: 152126 Hom.: 11742 Cov.: 33 AF XY: 0.388 AC XY: 28843 AN XY: 74368

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.410

Alfa AF: 0.240 Hom.: 565

Bravo AF: 0.362

Asia WGS AF: 0.551 AC: 1919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.39

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: rs3730668; hg19: chr18-51795847; COSMIC: COSV54190947; COSMIC: COSV54190947;