rs6800901

Positions:

• chr3-121435346-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199420.4(POLQ):​c.7543+776G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,974 control chromosomes in the GnomAD database, including 5,695 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 0.26 (5695 hom., cov: 32)
• Consequence: POLQ NM_199420.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLQ	NM_199420.4	c.7543+776G>A		intron_variant		ENST00000264233.6	NP_955452.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLQ	ENST00000264233.6	c.7543+776G>A		intron_variant		1	NM_199420.4	ENSP00000264233	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39616 AN: 151854 Hom.: 5698 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.261 AC: 39621 AN: 151974 Hom.: 5695 Cov.: 32 AF XY: 0.259 AC XY: 19222 AN XY: 74272

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.279

Alfa AF: 0.324 Hom.: 10762

Bravo AF: 0.254

Asia WGS AF: 0.168 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.51

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: rs6800901; hg19: chr3-121154193;