chr19-50402227-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000440232.7(POLD1):​c.612C>T​(p.His204=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 1,586,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

POLD1
ENST00000440232.7 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.795
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 19-50402227-C-T is Benign according to our data. Variant chr19-50402227-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 239360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.795 with no splicing effect.
BS2
High AC in GnomAd4 at 112 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
POLD1NM_002691.4 linkuse as main transcriptc.612C>T p.His204= synonymous_variant 6/27 ENST00000440232.7 NP_002682.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
POLD1ENST00000440232.7 linkuse as main transcriptc.612C>T p.His204= synonymous_variant 6/271 NM_002691.4 ENSP00000406046 P1

Frequencies

GnomAD3 genomes
AF:
0.000729
AC:
111
AN:
152250
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00244
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000153
AC:
35
AN:
228340
Hom.:
0
AF XY:
0.000155
AC XY:
19
AN XY:
122802
show subpopulations
Gnomad AFR exome
AF:
0.00169
Gnomad AMR exome
AF:
0.000125
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000554
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000290
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000934
AC:
134
AN:
1434596
Hom.:
0
Cov.:
34
AF XY:
0.0000788
AC XY:
56
AN XY:
710584
show subpopulations
Gnomad4 AFR exome
AF:
0.00228
Gnomad4 AMR exome
AF:
0.000309
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000368
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000164
Gnomad4 OTH exome
AF:
0.000389
GnomAD4 genome
AF:
0.000735
AC:
112
AN:
152368
Hom.:
0
Cov.:
33
AF XY:
0.000752
AC XY:
56
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.00245
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000823
Hom.:
0
Bravo
AF:
0.000918

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
Likely benign, criteria provided, single submitterclinical testingCenter for Genomic Medicine, Rigshospitalet, Copenhagen University HospitalAug 15, 2023- -
Benign, criteria provided, single submitterclinical testingWomen's Health and Genetics/Laboratory Corporation of America, LabCorpJul 13, 2023- -
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJan 04, 2022- -
Likely benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Feb 23, 2018- -
not provided Benign:3
Likely benign, criteria provided, single submitterclinical testingGeneDxOct 22, 2024See Variant Classification Assertion Criteria. -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingQuest Diagnostics Nichols Institute San Juan CapistranoMay 09, 2018- -
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsAug 17, 2015This 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. -
Likely benign, criteria provided, single submittercurationSema4, Sema4Mar 18, 2021- -
Colorectal cancer, susceptibility to, 10 Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 28, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
1.2
DANN
Benign
0.91
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.

Other links and lift over

dbSNP: rs147881471; hg19: chr19-50905484; COSMIC: COSV101486774; COSMIC: COSV101486774; API