rs6830513

Positions:

• chr4-2179353-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_181808.4(POLN):​c.1134A>G​(p.Thr378=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,611,502 control chromosomes in the GnomAD database, including 24,710 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 0.25 (7155 hom., cov: 32)
  • Exomes 𝑓: 0.13 (17555 hom.)
• Consequence: POLN NM_181808.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLN	NM_181808.4	c.1134A>G	p.Thr378=	synonymous_variant	8/26	ENST00000511885.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLN	ENST00000511885.6	c.1134A>G	p.Thr378=	synonymous_variant	8/26	5	NM_181808.4	P1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37469 AN: 152066 Hom.: 7137 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0843

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.249

GnomAD3 exomes AF: 0.186 AC: 46810 AN: 251210 Hom.: 6259 AF XY: 0.174 AC XY: 23634 AN XY: 135808

Gnomad AFR exome AF: 0.520

Gnomad AMR exome AF: 0.254

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.393

Gnomad SAS exome AF: 0.154

Gnomad FIN exome AF: 0.0943

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.178

GnomAD4 exome AF: 0.129 AC: 188416 AN: 1459318 Hom.: 17555 Cov.: 32 AF XY: 0.129 AC XY: 93331 AN XY: 726144

Gnomad4 AFR exome AF: 0.532

Gnomad4 AMR exome AF: 0.255

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.0929

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.247 AC: 37539 AN: 152184 Hom.: 7155 Cov.: 32 AF XY: 0.245 AC XY: 18201 AN XY: 74410

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.0843

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.251

Alfa AF: 0.143 Hom.: 5111

Bravo AF: 0.273

Asia WGS AF: 0.329 AC: 1145 AN: 3478

EpiCase AF: 0.123

EpiControl AF: 0.127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.26

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: rs6830513; hg19: chr4-2181080; COSMIC: COSV67026845;