rs3902018

chr11-74558772-C-T

Variant summary

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

The ENST00000528481.5(POLD3):c.-57-35289C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,200 control chromosomes in the GnomAD database, including 2,063 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 0.15 (2063 hom., cov: 32)
• Consequence: POLD3 ENST00000528481.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228

Genes affected

POLD3 (HGNC:20932): (DNA polymerase delta 3, accessory subunit) This gene encodes the 66-kDa subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. The encoded protein plays a role in regulating the activity of DNA polymerase delta through interactions with other subunits and the processivity cofactor proliferating cell nuclear antigen (PCNA). Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLD3	ENST00000528481.5	c.-57-35289C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23564 AN: 152082 Hom.: 2067 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0992

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.0833

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.155 AC: 23567 AN: 152200 Hom.: 2063 Cov.: 32 AF XY: 0.157 AC XY: 11687 AN XY: 74406

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.0990

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.0824

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.136

Alfa AF: 0.126 Hom.: 1573

Bravo AF: 0.152

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	12
Dann	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3902018; hg19: chr11-74269817;