19-50398570-CAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAA

Variant names:

• chr19-50398570-C-CAAA
• rs35689550
• NM_002691.4:c.-1-261_-1-259dupAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002691.4(POLD1):​c.-1-261_-1-259dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0089 (23 hom., cov: 0)
• Consequence: POLD1 NM_002691.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.527

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00887 (554/62426) while in subpopulation AFR AF= 0.0199 (285/14334). AF 95% confidence interval is 0.018. There are 23 homozygotes in gnomad4. There are 263 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 554 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLD1	NM_002691.4	c.-1-261_-1-259dupAAA		intron_variant	Intron 1 of 26	ENST00000440232.7	NP_002682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLD1	ENST00000440232.7	c.-1-281_-1-280insAAA		intron_variant	Intron 1 of 26	1	NM_002691.4	ENSP00000406046.1

Frequencies

GnomAD3 genomes AF: 0.00886 AC: 553 AN: 62404 Hom.: 23 Cov.: 0

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.00772

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00763

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.00575

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00430

Gnomad OTH AF: 0.00838

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

GnomAD4 genome AF: 0.00887 AC: 554 AN: 62426 Hom.: 23 Cov.: 0 AF XY: 0.00992 AC XY: 263 AN XY: 26508

Gnomad4 AFR AF: 0.0199

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.00763

Gnomad4 EAS AF: 0.0155

Gnomad4 SAS AF: 0.00578

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00430

Gnomad4 OTH AF: 0.00838

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35689550; hg19: chr19-50901827;