19-50398595-A-G

Position:

• chr19-50398595-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002691.4(POLD1):​c.-1-256A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 133,142 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.017 (46 hom., cov: 30)
• Consequence: POLD1 NM_002691.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.597

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-50398595-A-G is Benign according to our data. Variant chr19-50398595-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1214218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0171 (2276/133142) while in subpopulation NFE AF= 0.026 (1621/62258). AF 95% confidence interval is 0.025. There are 46 homozygotes in gnomad4. There are 1021 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2276 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLD1	NM_002691.4	c.-1-256A>G		intron_variant		ENST00000440232.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLD1	ENST00000440232.7	c.-1-256A>G		intron_variant		1	NM_002691.4	P1

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2279 AN: 133084 Hom.: 46 Cov.: 30

Gnomad AFR AF: 0.00499

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0210

Gnomad ASJ AF: 0.0310

Gnomad EAS AF: 0.000704

Gnomad SAS AF: 0.00609

Gnomad FIN AF: 0.00316

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0260

Gnomad OTH AF: 0.0233

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0171 AC: 2276 AN: 133142 Hom.: 46 Cov.: 30 AF XY: 0.0159 AC XY: 1021 AN XY: 64022

Gnomad4 AFR AF: 0.00495

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.0310

Gnomad4 EAS AF: 0.000704

Gnomad4 SAS AF: 0.00638

Gnomad4 FIN AF: 0.00316

Gnomad4 NFE AF: 0.0260

Gnomad4 OTH AF: 0.0231

Alfa AF: 0.00860 Hom.: 2

Bravo AF: 0.0170

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.63
DANN	Benign	0.32

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

Other links and lift over

dbSNP: rs3219362; hg19: chr19-50901852;