chr19-50398636-G-A

Position:

• chr19-50398636-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002691.4(POLD1):​c.-1-215G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 150,460 control chromosomes in the GnomAD database, including 2,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (2039 hom., cov: 31)
• Consequence: POLD1 NM_002691.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.310

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=-0.92).
• BP6: Variant 19-50398636-G-A is Benign according to our data. Variant chr19-50398636-G-A is described in ClinVar as [Benign]. Clinvar id is 1229647.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLD1	NM_002691.4	c.-1-215G>A		intron_variant		ENST00000440232.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLD1	ENST00000440232.7	c.-1-215G>A		intron_variant		1	NM_002691.4	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20214 AN: 150364 Hom.: 2032 Cov.: 31

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0975

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0339

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0669

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.135 AC: 20248 AN: 150460 Hom.: 2039 Cov.: 31 AF XY: 0.133 AC XY: 9783 AN XY: 73348

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.0972

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.0339

Gnomad4 NFE AF: 0.0669

Gnomad4 OTH AF: 0.123

Alfa AF: 0.106 Hom.: 201

Bravo AF: 0.146

Asia WGS AF: 0.184 AC: 638 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.48

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: rs1673026; hg19: chr19-50901893;