18-54269477-G-T

Variant names:

• chr18-54269477-G-T
• rs3730668
• ENST00000621167.1:n.552C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	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 rank	TSL	MANE	Protein	Appris	UniProt
POLI	ENST00000579534.6	c.-70G>T		upstream_gene_variant		1	NM_007195.3	ENSP00000462664.1

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

African (AFR) AF: 0.212 AC: 5409 AN: 25468

American (AMR) AF: 0.399 AC: 8153 AN: 20444

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 10952 AN: 22442

East Asian (EAS) AF: 0.711 AC: 21374 AN: 30052

South Asian (SAS) AF: 0.493 AC: 35491 AN: 72030

European-Finnish (FIN) AF: 0.478 AC: 20457 AN: 42820

Middle Eastern (MID) AF: 0.465 AC: 2028 AN: 4364

European-Non Finnish (NFE) AF: 0.403 AC: 425098 AN: 1055802

Other (OTH) AF: 0.429 AC: 23595 AN: 55006

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

African (AFR) AF: 0.223 AC: 9269 AN: 41544

American (AMR) AF: 0.409 AC: 6257 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1694 AN: 3472

East Asian (EAS) AF: 0.682 AC: 3515 AN: 5156

South Asian (SAS) AF: 0.510 AC: 2459 AN: 4824

European-Finnish (FIN) AF: 0.514 AC: 5433 AN: 10570

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27588 AN: 67966

Other (OTH) AF: 0.410 AC: 866 AN: 2112

Alfa AF: 0.240 Hom.: 587

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
PhyloP100		0.83
PromoterAI		0.015	Neutral
Mutation Taster		=300/0	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: rs3730668; hg19: chr18-51795847; COSMIC: COSV54190947; COSMIC: COSV54190947;