Variant rs149096523 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_002691.4(POLD1):c.714G>A(p.Thr238=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 1,610,868 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 1 hom. )

Consequence

POLD1
NM_002691.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.389

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 19-50402329-G-A is Benign according to our data. Variant chr19-50402329-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 220847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50402329-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.389 with no splicing effect.

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLD1	NM_002691.4 linkuse as main transcript	c.714G>A	p.Thr238=	synonymous_variant	6/27	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7 linkuse as main transcript	c.714G>A	p.Thr238=	synonymous_variant	6/27	1	NM_002691.4	ENSP00000406046	P1

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000411

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000207

AC:

AN:

246412

Hom.:

AF XY:

0.000187

AC XY:

AN XY:

133582

show subpopulations

Gnomad AFR exome

AF:

0.000127

Gnomad AMR exome

AF:

0.000379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000553

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000298

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000420

AC:

613

AN:

1458490

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

282

AN XY:

725046

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000472

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000502

Gnomad4 OTH exome

AF:

0.000465

GnomAD4 genome

AF:

0.000289

AC:

AN:

152378

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000168

Hom.:

Bravo

AF:

0.000310

EpiCase

AF:

0.000763

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	POLD1: BP4, BP7 -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 12, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 20, 2021	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Jun 21, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 21, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 28, 2018	- -

Colorectal cancer, susceptibility to, 10

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Hereditary cancer-predisposing syndrome

Benign:2

Benign, criteria provided, single submitter	curation	Sema4, Sema4	Mar 24, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 07, 2015	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.8

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

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