rs929313

chrX-24729032-A-CchrX-24729032-A-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001330360.2(POLA1):c.1686+1096A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.52 (10997 hom., 16835 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: POLA1 NM_001330360.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

Genes affected

POLA1 (HGNC:9173): (DNA polymerase alpha 1, catalytic subunit) This gene encodes the catalytic subunit of DNA polymerase, which together with a regulatory and two primase subunits, forms the DNA polymerase alpha complex. The catalytic subunit plays an essential role in the initiation of DNA replication. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High Homozygotes in GnomAd at 11005 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLA1	NM_001330360.2	c.1686+1096A>C		intron_variant		ENST00000379068.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLA1	ENST00000379068.8	c.1686+1096A>C		intron_variant		5	NM_001330360.2	A1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 57060 AN: 110757 Hom.: 11005 Cov.: 23 AF XY: 0.510 AC XY: 16808 AN XY: 32989

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.517

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.540

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.515 AC: 57080 AN: 110810 Hom.: 10997 Cov.: 23 AF XY: 0.509 AC XY: 16835 AN XY: 33052

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.538

Alfa AF: 0.585 Hom.: 51346

Bravo AF: 0.515

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.46
Dann	Benign	0.75

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: rs929313; hg19: chrX-24747149;