Variant 4-2072975-TG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_181808.4(POLN):c.2509del(p.Gln837SerfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00581 in 1,613,342 control chromosomes in the GnomAD database, including 217 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 213 hom. )

Consequence

POLN
NM_181808.4 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.675

Variant links:

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]

POLN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 4-2072975-TG-T is Benign according to our data. Variant chr4-2072975-TG-T is described in ClinVar as [Benign]. Clinvar id is 715710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.093 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLN	NM_181808.4 linkuse as main transcript	c.2509del	p.Gln837SerfsTer8	frameshift_variant	25/26	ENST00000511885.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLN	ENST00000511885.6 linkuse as main transcript	c.2509del	p.Gln837SerfsTer8	frameshift_variant	25/26	5	NM_181808.4	P1	Q7Z5Q5-1

Frequencies

GnomAD3 genomes

AF:

0.00441

AC:

671

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.0546

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00326

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00713

AC:

1791

AN:

251032

Hom.:

AF XY:

0.00664

AC XY:

902

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.0513

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.00131

Gnomad NFE exome

AF:

0.00267

Gnomad OTH exome

AF:

0.00669

GnomAD4 exome

AF:

0.00596

AC:

8713

AN:

1461050

Hom.:

213

Cov.:

AF XY:

0.00581

AC XY:

4221

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.0105

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.0956

Gnomad4 SAS exome

AF:

0.00118

Gnomad4 FIN exome

AF:

0.00195

Gnomad4 NFE exome

AF:

0.00337

Gnomad4 OTH exome

AF:

0.00634

GnomAD4 genome

AF:

0.00439

AC:

668

AN:

152292

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.0549

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00326

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00353

Hom.:

Bravo

AF:

0.00512

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.00316

EpiControl

AF:

0.00314

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2019	This variant is associated with the following publications: (PMID: 29074453) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over