19-50384211-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000600859.5(POLD1):​n.-181C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00364 in 152,252 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 9 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

POLD1
ENST00000600859.5 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.332
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 -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 19-50384211-C-G is Benign according to our data. Variant chr19-50384211-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1190137.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 554 AD gene.

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
POLD1ENST00000600859.5 linkn.-181C>G 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 26 2 ENSP00000470726.1 M0QZR8
POLD1ENST00000600859.5 linkn.-181C>G non_coding_transcript_exon_variant Exon 1 of 26 2 ENSP00000470726.1 M0QZR8
POLD1ENST00000600859.5 linkn.-181C>G 5_prime_UTR_variant Exon 1 of 26 2 ENSP00000470726.1 M0QZR8

Frequencies

GnomAD3 genomes
AF:
0.00363
AC:
553
AN:
152134
Hom.:
9
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0128
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000955
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
144
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
116
Gnomad4 AMR exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00364
AC:
554
AN:
152252
Hom.:
9
Cov.:
33
AF XY:
0.00376
AC XY:
280
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0128
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.000279
Hom.:
0
Bravo
AF:
0.00386
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 02, 2018
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
2.4
DANN
Benign
0.43

Splicing

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: rs3219284; hg19: chr19-50887468; API