19-50406132-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002691.4(POLD1):c.1243-50T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 1,588,260 control chromosomes in the GnomAD database, including 457,142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 47349 hom., cov: 32)

Exomes 𝑓: 0.75 ( 409793 hom. )

Consequence

POLD1
NM_002691.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.300

Publications

25 publications found

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 Gene-Disease associations (from GenCC):

POLD1-related polyposis and colorectal cancer syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
colorectal cancer, susceptibility to, 10
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
mandibular hypoplasia-deafness-progeroid syndrome
Inheritance: AD, AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, Ambry Genetics, Orphanet, G2P
Polymerase proofreading-related adenomatous polyposis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
immunodeficiency 120
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
non-severe combined immunodeficiency due to polymerase delta deficiency
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

POLD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 19-50406132-T-G is Benign according to our data. Variant chr19-50406132-T-G is described in ClinVar as Benign. ClinVar VariationId is 676483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002691.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POLD1	NM_002691.4	MANE Select	c.1243-50T>G	intron	N/A	NP_002682.2
POLD1	NM_001308632.1		c.1243-50T>G	intron	N/A	NP_001295561.1
POLD1	NM_001256849.1		c.1243-50T>G	intron	N/A	NP_001243778.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
POLD1	ENST00000440232.7	TSL:1 MANE Select	c.1243-50T>G	intron	N/A	ENSP00000406046.1
POLD1	ENST00000595904.6	TSL:1	c.1243-50T>G	intron	N/A	ENSP00000472445.1
POLD1	ENST00000599857.7	TSL:1	c.1243-50T>G	intron	N/A	ENSP00000473052.1

Frequencies

GnomAD3 genomes

AF:

0.780

AC:

118518

AN:

151936

Hom.:

47296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.900

Gnomad AMI

AF:

0.740

Gnomad AMR

AF:

0.787

Gnomad ASJ

AF:

0.643

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.700

Gnomad FIN

AF:

0.739

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.739

GnomAD2 exomes

AF:

0.731

AC:

174621

AN:

238954

AF XY:

0.726

show subpopulations

Gnomad AFR exome

AF:

0.908

Gnomad AMR exome

AF:

0.834

Gnomad ASJ exome

AF:

0.641

Gnomad EAS exome

AF:

0.278

Gnomad FIN exome

AF:

0.740

Gnomad NFE exome

AF:

0.763

Gnomad OTH exome

AF:

0.733

GnomAD4 exome

AF:

0.750

AC:

1077099

AN:

1436206

Hom.:

409793

Cov.:

AF XY:

0.748

AC XY:

531451

AN XY:

710672

show subpopulations

African (AFR)

AF:

0.904

AC:

29958

AN:

33128

American (AMR)

AF:

0.829

AC:

36340

AN:

43834

Ashkenazi Jewish (ASJ)

AF:

0.645

AC:

16011

AN:

24810

East Asian (EAS)

AF:

0.285

AC:

11197

AN:

39250

South Asian (SAS)

AF:

0.703

AC:

58803

AN:

83662

European-Finnish (FIN)

AF:

0.741

AC:

38146

AN:

51474

Middle Eastern (MID)

AF:

0.741

AC:

4199

AN:

5666

European-Non Finnish (NFE)

AF:

0.767

AC:

839473

AN:

1095066

Other (OTH)

AF:

0.724

AC:

42972

AN:

59316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

13885

27771

41656

55542

69427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20324

40648

60972

81296

101620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.780

AC:

118633

AN:

152054

Hom.:

47349

Cov.:

AF XY:

0.775

AC XY:

57628

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.900

AC:

37348

AN:

41496

American (AMR)

AF:

0.787

AC:

12025

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.643

AC:

2228

AN:

3464

East Asian (EAS)

AF:

0.295

AC:

1515

AN:

5138

South Asian (SAS)

AF:

0.700

AC:

3373

AN:

4822

European-Finnish (FIN)

AF:

0.739

AC:

7816

AN:

10570

Middle Eastern (MID)

AF:

0.755

AC:

222

AN:

294

European-Non Finnish (NFE)

AF:

0.763

AC:

51879

AN:

67962

Other (OTH)

AF:

0.737

AC:

1557

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1288

2576

3863

5151

6439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.769

Hom.:

43043

Bravo

AF:

0.787

Asia WGS

AF:

0.555

AC:

1933

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hereditary cancer-predisposing syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

8.5

(source)

DANN

Benign

0.76

PhyloP100

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over