rs17132382

Variant names:

• chr4-2234472-C-T
• rs17132382
• NM_181808.4:c.-12-5229G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

Genes affected

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]

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]

ENSG00000290263 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
POLN	NM_181808.4	c.-12-5229G>A		intron_variant	Intron 2 of 25	ENST00000511885.6	NP_861524.2
HAUS3	NM_001303143.2	c.1578+1756G>A		intron_variant	Intron 5 of 5	ENST00000443786.3	NP_001290072.1
COX6B1P5		n.2234472C>T		intragenic_variant
HAUS3	NM_024511.7	c.1578+1756G>A		intron_variant	Intron 4 of 4		NP_078787.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLN	ENST00000511885.6	c.-12-5229G>A		intron_variant	Intron 2 of 25	5	NM_181808.4	ENSP00000435506.1
HAUS3	ENST00000443786.3	c.1578+1756G>A		intron_variant	Intron 5 of 5	1	NM_001303143.2	ENSP00000392903.2
ENSG00000290263	ENST00000672725.1	n.1578+1756G>A		intron_variant	Intron 4 of 18			ENSP00000500518.1

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

African (AFR) AF: 0.386 AC: 17 AN: 44

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.375 AC: 3 AN: 8

South Asian (SAS) AF: 0.125 AC: 3 AN: 24

European-Finnish (FIN) AF: 0.0463 AC: 5 AN: 108

Middle Eastern (MID) AF: 0.120 AC: 76 AN: 632

European-Non Finnish (NFE) AF: 0.0539 AC: 18 AN: 334

Other (OTH) AF: 0.217 AC: 23 AN: 106

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

African (AFR) AF: 0.367 AC: 15219 AN: 41432

American (AMR) AF: 0.170 AC: 2596 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3472

East Asian (EAS) AF: 0.348 AC: 1800 AN: 5170

South Asian (SAS) AF: 0.120 AC: 577 AN: 4818

European-Finnish (FIN) AF: 0.0302 AC: 321 AN: 10614

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0584 AC: 3974 AN: 68008

Other (OTH) AF: 0.176 AC: 371 AN: 2110

Alfa AF: 0.129 Hom.: 386

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
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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