rs17132382

chr4-2234472-C-T

Variant summary

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

The NM_181808.4(POLN):c.-12-5229G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 153,362 control chromosomes in the GnomAD database, including 3,617 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 0.17 (3600 hom., cov: 32)
  • Exomes 𝑓: 0.12 (17 hom.)
• Consequence: POLN NM_181808.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

Genes affected

HAUS3 (HGNC:28719): (HAUS augmin like complex subunit 3) This gene encodes a component of the HAUS augmin-like protein complex, which plays a key role in cytokinesis and mitosis. Disruption of the encoded protein causes mitotic defects resulting from fragmentation of centrosomes and microtubule destabilization. This gene shares its 5' exons with some transcripts from overlapping GeneID: 353497, which encodes a DNA polymerase. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

POLN (HGNC:18870): (DNA polymerase nu) This gene encodes a DNA polymerase type-A family member. The encoded protein plays a role in DNA repair and homologous recombination. This gene shares its 5' exons with some transcripts from overlapping GeneID: 79441, which encodes an augmentin-like protein complex subunit. [provided by RefSeq, Dec 2014]

COX6B1P5 (HGNC:37675): (cytochrome c oxidase subunit 6B1 pseudogene 5)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAUS3	NM_001303143.2	c.1578+1756G>A		intron_variant		ENST00000443786.3
POLN	NM_181808.4	c.-12-5229G>A		intron_variant		ENST00000511885.6
HAUS3	NM_024511.7	c.1578+1756G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAUS3	ENST00000443786.3	c.1578+1756G>A		intron_variant		1	NM_001303143.2	P1
POLN	ENST00000511885.6	c.-12-5229G>A		intron_variant		5	NM_181808.4	P1
COX6B1P5	ENST00000509843.2	n.222C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25218 AN: 151984 Hom.: 3590 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0584

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.115 AC: 145 AN: 1258 Hom.: 17 Cov.: 0 AF XY: 0.108 AC XY: 78 AN XY: 720

Gnomad4 AFR exome AF: 0.386

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0463

Gnomad4 NFE exome AF: 0.0539

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.166 AC: 25263 AN: 152104 Hom.: 3600 Cov.: 32 AF XY: 0.165 AC XY: 12250 AN XY: 74372

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0302

Gnomad4 NFE AF: 0.0584

Gnomad4 OTH AF: 0.176

Alfa AF: 0.123 Hom.: 335

Bravo AF: 0.191

Asia WGS AF: 0.272 AC: 947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.0
Dann	Benign	0.68

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: rs17132382; hg19: chr4-2236199; COSMIC: COSV71319272; COSMIC: COSV71319272;