chr11-74558772-C-T

Variant names:

• chr11-74558772-C-T
• rs3902018
• ENST00000528481.5:c.-57-35289C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

POLD3 Gene-Disease associations (from GenCC):

• hearing loss disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLD3	ENST00000528481.5	c.-57-35289C>T		intron_variant	Intron 1 of 5	2		ENSP00000431239.1

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

African (AFR) AF: 0.242 AC: 10055 AN: 41504

American (AMR) AF: 0.0990 AC: 1516 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0764 AC: 265 AN: 3470

East Asian (EAS) AF: 0.0824 AC: 427 AN: 5184

South Asian (SAS) AF: 0.205 AC: 991 AN: 4826

European-Finnish (FIN) AF: 0.169 AC: 1783 AN: 10576

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8092 AN: 68014

Other (OTH) AF: 0.136 AC: 288 AN: 2114

Alfa AF: 0.127 Hom.: 2100

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
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs3902018; hg19: chr11-74269817;