chr3-121520180-G-A

Position:

• chr3-121520180-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
POLQ	NM_199420.4	c.1256-97C>T		intron_variant		ENST00000264233.6	NP_955452.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLQ	ENST00000264233.6	c.1256-97C>T		intron_variant		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

Gnomad4 AFR exome AF: 0.845

Gnomad4 AMR exome AF: 0.760

Gnomad4 ASJ exome AF: 0.766

Gnomad4 EAS exome AF: 0.891

Gnomad4 SAS exome AF: 0.881

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.752

Gnomad4 OTH exome AF: 0.780

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

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.890

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.784

Alfa AF: 0.762 Hom.: 74183

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

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: rs702019; hg19: chr3-121239027;