dbSNP rs3219433: POLD1:c.2718-12A>C (chr19-50415712-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002691.4(POLD1):c.2718-12A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0087 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000032 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

POLD1
NM_002691.4 intron

Scores

Splicing: ADA: 0.00001998

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.90

Variant links:

Genes affected

POLD1 (HGNC:9175): (DNA polymerase delta 1, catalytic subunit) This gene encodes the 125-kDa catalytic 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. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Mar 2012]

POLD1 links:

ENSG00000142539 (HGNC:):

ENSG00000142539 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLD1	NM_002691.4 link	c.2718-12A>C		intron_variant	Intron 21 of 26	ENST00000440232.7	NP_002682.2	P28340A0A024R4F4Q59FA0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7 link	c.2718-12A>C		intron_variant	Intron 21 of 26	1	NM_002691.4	ENSP00000406046.1		P28340
ENSG00000142539	ENST00000599632.1 link	c.-88A>C		upstream_gene_variant		5		ENSP00000473233.1		M0R3H8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

533

AN:

61056

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00316

Gnomad AMI

AF:

0.0145

Gnomad AMR

AF:

0.00830

Gnomad ASJ

AF:

0.00781

Gnomad EAS

AF:

0.00226

Gnomad SAS

AF:

0.00341

Gnomad FIN

AF:

0.0159

Gnomad MID

AF:

0.00794

Gnomad NFE

AF:

0.0209

Gnomad OTH

AF:

0.00358

GnomAD3 exomes

AF:

0.000169

AC:

AN:

118132

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

64506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000500

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000117

Gnomad SAS exome

AF:

0.000361

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000221

Gnomad OTH exome

AF:

0.000595

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000323

AC:

AN:

896936

Hom.:

Cov.:

AF XY:

0.0000246

AC XY:

AN XY:

446350

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000363

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000619

Gnomad4 FIN exome

AF:

0.000108

Gnomad4 NFE exome

AF:

0.0000322

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00871

AC:

533

AN:

61182

Hom.:

Cov.:

AF XY:

0.00824

AC XY:

246

AN XY:

29842

show subpopulations

Gnomad4 AFR

AF:

0.00315

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.00781

Gnomad4 EAS

AF:

0.00225

Gnomad4 SAS

AF:

0.00341

Gnomad4 FIN

AF:

0.0159

Gnomad4 NFE

AF:

0.0208

Gnomad4 OTH

AF:

0.00350

Alfa

AF:

0.000222

Hom.:

376

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome

Uncertain:1

Oct 08, 2015

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2718-12A>C intronic alteration consists of a A to C substitution 12 nucleotides before coding exon 21 in the POLD1 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.40

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000020

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over