chr18-54284454-C-T

Variant names:

• chr18-54284454-C-T
• rs476630
• NM_007195.3:c.1067+441C>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.1067+441C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,076 control chromosomes in the GnomAD database, including 5,099 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 (5091 hom., cov: 32)
  • Exomes 𝑓: 0.40 (8 hom.)
• Consequence: POLI NM_007195.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLI	NM_007195.3	c.1067+441C>T		intron_variant	Intron 7 of 9	ENST00000579534.6	NP_009126.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLI	ENST00000579534.6	c.1067+441C>T		intron_variant	Intron 7 of 9	1	NM_007195.3	ENSP00000462664.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38505 AN: 151832 Hom.: 5092 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.0294

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

GnomAD4 exome AF: 0.397 AC: 50 AN: 126 Hom.: 8 AF XY: 0.338 AC XY: 27 AN XY: 80

African (AFR) AF: 0.375 AC: 3 AN: 8

American (AMR) AF: 0.167 AC: 2 AN: 12

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.422 AC: 43 AN: 102

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.253 AC: 38512 AN: 151950 Hom.: 5091 Cov.: 32 AF XY: 0.249 AC XY: 18514 AN XY: 74270

African (AFR) AF: 0.236 AC: 9778 AN: 41410

American (AMR) AF: 0.222 AC: 3388 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3472

East Asian (EAS) AF: 0.0293 AC: 152 AN: 5188

South Asian (SAS) AF: 0.248 AC: 1196 AN: 4820

European-Finnish (FIN) AF: 0.222 AC: 2337 AN: 10550

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19789 AN: 67950

Other (OTH) AF: 0.259 AC: 547 AN: 2112

Alfa AF: 0.161 Hom.: 331

Bravo AF: 0.251

Asia WGS AF: 0.155 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		-0.0070
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: rs476630; hg19: chr18-51810824;