rs669277

Positions:

• chr3-121460823-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_199420.4(POLQ):​c.6968-589A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0982 in 152,062 control chromosomes in the GnomAD database, including 1,061 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 0.098 (1061 hom., cov: 32)
• Consequence: POLQ NM_199420.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLQ	NM_199420.4	c.6968-589A>G		intron_variant		ENST00000264233.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLQ	ENST00000264233.6	c.6968-589A>G		intron_variant		1	NM_199420.4	P1
POLQ	ENST00000474243.1	n.468+6696A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14910 AN: 151944 Hom.: 1056 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0593

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.0952

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0982 AC: 14934 AN: 152062 Hom.: 1061 Cov.: 32 AF XY: 0.0953 AC XY: 7086 AN XY: 74336

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0629

Gnomad4 ASJ AF: 0.0787

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0593

Gnomad4 NFE AF: 0.0691

Gnomad4 OTH AF: 0.0942

Alfa AF: 0.0944 Hom.: 100

Bravo AF: 0.104

Asia WGS AF: 0.0250 AC: 89 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.8
DANN	Benign	0.92

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: rs669277; hg19: chr3-121179670;