rs702019

Variant names:

• chr3-121520180-G-A
• rs702019
• NM_199420.4:c.1256-97C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199420.4(POLQ):​c.1256-97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 697,712 control chromosomes in the GnomAD database, including 212,507 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 0.79 (47549 hom., cov: 31)
  • Exomes 𝑓: 0.78 (164958 hom.)
• Consequence: POLQ NM_199420.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 9 publications found

Genes affected

POLQ (HGNC:9186): (DNA polymerase theta) Enables catalytic activity, acting on DNA; chromatin binding activity; and identical protein binding activity. Involved in DNA repair; negative regulation of double-strand break repair via homologous recombination; and protein homooligomerization. Located in Golgi apparatus; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLQ	NM_199420.4	c.1256-97C>T		intron_variant	Intron 8 of 29	ENST00000264233.6	NP_955452.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLQ	ENST00000264233.6	c.1256-97C>T		intron_variant	Intron 8 of 29	1	NM_199420.4	ENSP00000264233.5

Frequencies

GnomAD3 genomes AF: 0.790 AC: 119977 AN: 151960 Hom.: 47498 Cov.: 31

Gnomad AFR AF: 0.848

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.783

GnomAD4 exome AF: 0.776 AC: 423328 AN: 545634 Hom.: 164958 AF XY: 0.780 AC XY: 226674 AN XY: 290528

African (AFR) AF: 0.845 AC: 11678 AN: 13816

American (AMR) AF: 0.760 AC: 17732 AN: 23322

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 12343 AN: 16114

East Asian (EAS) AF: 0.891 AC: 28426 AN: 31918

South Asian (SAS) AF: 0.881 AC: 44044 AN: 49982

European-Finnish (FIN) AF: 0.741 AC: 33777 AN: 45574

Middle Eastern (MID) AF: 0.805 AC: 1766 AN: 2194

European-Non Finnish (NFE) AF: 0.752 AC: 250712 AN: 333430

Other (OTH) AF: 0.780 AC: 22850 AN: 29284

GnomAD4 genome AF: 0.790 AC: 120088 AN: 152078 Hom.: 47549 Cov.: 31 AF XY: 0.793 AC XY: 58955 AN XY: 74298

African (AFR) AF: 0.849 AC: 35231 AN: 41508

American (AMR) AF: 0.773 AC: 11806 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2628 AN: 3468

East Asian (EAS) AF: 0.890 AC: 4594 AN: 5162

South Asian (SAS) AF: 0.877 AC: 4224 AN: 4818

European-Finnish (FIN) AF: 0.750 AC: 7907 AN: 10548

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51089 AN: 67982

Other (OTH) AF: 0.784 AC: 1652 AN: 2108

Alfa AF: 0.768 Hom.: 124240

Bravo AF: 0.792

Asia WGS AF: 0.864 AC: 3005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.61
DANN	Benign	0.63
PhyloP100		-0.24
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: rs702019; hg19: chr3-121239027;