Variant 2-74958847-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_019896.4(POLE4):c.168G>A(p.Val56=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,561,440 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0070 ( 42 hom. )

Consequence

POLE4
NM_019896.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.598

Variant links:

Genes affected

POLE4 (HGNC:18755): (DNA polymerase epsilon 4, accessory subunit) POLE4 is a histone-fold protein that interacts with other histone-fold proteins to bind DNA in a sequence-independent manner. These histone-fold protein dimers combine within larger enzymatic complexes for DNA transcription, replication, and packaging.[supplied by OMIM, Apr 2004]

POLE4 links:

LOC105374809 (HGNC:):

LOC105374809 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 2-74958847-G-A is Benign according to our data. Variant chr2-74958847-G-A is described in ClinVar as [Benign]. Clinvar id is 774287.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.598 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
POLE4	NM_019896.4 linkuse as main transcript	c.168G>A	p.Val56=	synonymous_variant	1/4	ENST00000483063.2
LOC105374809	XR_002959406.2 linkuse as main transcript	n.33C>T		non_coding_transcript_exon_variant	1/2
LOC105374809	XR_007087109.1 linkuse as main transcript	n.33C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
POLE4	ENST00000483063.2 linkuse as main transcript	c.168G>A	p.Val56=	synonymous_variant	1/4	1	NM_019896.4	P1
POLE4	ENST00000233699.8 linkuse as main transcript	n.56G>A		non_coding_transcript_exon_variant	1/5	3
POLE4	ENST00000459636.5 linkuse as main transcript	n.142G>A		non_coding_transcript_exon_variant	1/4	3
POLE4	ENST00000485527.5 linkuse as main transcript	n.143G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00501

AC:

763

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00753

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00788

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00466

AC:

788

AN:

168988

Hom.:

AF XY:

0.00460

AC XY:

414

AN XY:

89912

show subpopulations

Gnomad AFR exome

AF:

0.00174

Gnomad AMR exome

AF:

0.00316

Gnomad ASJ exome

AF:

0.000229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000848

Gnomad FIN exome

AF:

0.00745

Gnomad NFE exome

AF:

0.00774

Gnomad OTH exome

AF:

0.00432

GnomAD4 exome

AF:

0.00697

AC:

9824

AN:

1409124

Hom.:

Cov.:

AF XY:

0.00684

AC XY:

4763

AN XY:

696152

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00371

Gnomad4 ASJ exome

AF:

0.000238

Gnomad4 EAS exome

AF:

0.0000275

Gnomad4 SAS exome

AF:

0.000963

Gnomad4 FIN exome

AF:

0.00681

Gnomad4 NFE exome

AF:

0.00819

Gnomad4 OTH exome

AF:

0.00530

GnomAD4 genome

AF:

0.00502

AC:

764

AN:

152316

Hom.:

Cov.:

AF XY:

0.00518

AC XY:

386

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00753

Gnomad4 NFE

AF:

0.00789

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00620

Hom.:

Bravo

AF:

0.00494

Asia WGS

AF:

0.00116

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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