chr19-50393103-T-C

Position:

• chr19-50393103-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002691.4(POLD1):​c.-1-5748T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,046 control chromosomes in the GnomAD database, including 32,619 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32619 hom., cov: 32)
• Consequence: POLD1 NM_002691.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLD1	NM_002691.4	c.-1-5748T>C		intron_variant		ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.-1-5748T>C		intron_variant		1	NM_002691.4	ENSP00000406046.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98325 AN: 151928 Hom.: 32552 Cov.: 32

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.648 AC: 98455 AN: 152046 Hom.: 32619 Cov.: 32 AF XY: 0.650 AC XY: 48297 AN XY: 74316

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.663

Alfa AF: 0.610 Hom.: 6897

Bravo AF: 0.655

Asia WGS AF: 0.775 AC: 2694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.23

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: rs2546551; hg19: chr19-50896360;