chrX-24966522-G-A

Position:

• chrX-24966522-G-A

Variant summary

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

The NM_001330360.2(POLA1):​c.4262-29283G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 111,903 control chromosomes in the GnomAD database, including 232 homozygotes. There are 1,382 hemizygotes in GnomAD. 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 0.046 (232 hom., 1382 hem., cov: 23)
• Consequence: POLA1 NM_001330360.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLA1	NM_001330360.2	c.4262-29283G>A		intron_variant		ENST00000379068.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLA1	ENST00000379068.8	c.4262-29283G>A		intron_variant		5	NM_001330360.2	A1

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 5149 AN: 111852 Hom.: 231 Cov.: 23 AF XY: 0.0403 AC XY: 1371 AN XY: 34060

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00729

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.00984

Gnomad EAS AF: 0.000278

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.00329

Gnomad MID AF: 0.0251

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0356

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

GnomAD4 genome AF: 0.0461 AC: 5163 AN: 111903 Hom.: 232 Cov.: 23 AF XY: 0.0405 AC XY: 1382 AN XY: 34121

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0211

Gnomad4 ASJ AF: 0.00984

Gnomad4 EAS AF: 0.000279

Gnomad4 SAS AF: 0.00749

Gnomad4 FIN AF: 0.00329

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.0352

Alfa AF: 0.0210 Hom.: 666

Bravo AF: 0.0532

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.30
DANN	Benign	0.42

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: rs10521932; hg19: chrX-24984639;