chr10-101580299-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001174084.2(POLL):c.1312C>T(p.Arg438Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,613,192 control chromosomes in the GnomAD database, including 33,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2392 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31057 hom. )

Consequence

POLL
NM_001174084.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.72

Publications

50 publications found

Variant links:

Genes affected

POLL (HGNC:9184): (DNA polymerase lambda) This gene encodes a DNA polymerase. DNA polymerases catalyze DNA-template-directed extension of the 3'-end of a DNA strand. This particular polymerase, which is a member of the X family of DNA polymerases, likely plays a role in non-homologous end joining and other DNA repair processes. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2010]

POLL links:

DPCD (HGNC:24542): (deleted in primary ciliary dyskinesia homolog (mouse)) This gene in mouse encodes a protein that may be involved in the generation and maintenance of ciliated cells. In mouse, expression of this gene increases during ciliated cell differentiation, and disruption of this gene has been linked to primary ciliary dyskinesia. [provided by RefSeq, Jul 2016]

DPCD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017029941).

BP6

Variant 10-101580299-G-A is Benign according to our data. Variant chr10-101580299-G-A is described in ClinVar as Benign. ClinVar VariationId is 1248188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174084.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
POLL	NM_001174084.2	MANE Select	c.1312C>T	p.Arg438Trp	missense	Exon 8 of 9	NP_001167555.1
POLL	NM_013274.4		c.1312C>T	p.Arg438Trp	missense	Exon 8 of 9	NP_037406.1
POLL	NM_001174085.2		c.1036C>T	p.Arg346Trp	missense	Exon 8 of 9	NP_001167556.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
POLL	ENST00000370162.8	TSL:1 MANE Select	c.1312C>T	p.Arg438Trp	missense	Exon 8 of 9	ENSP00000359181.3
POLL	ENST00000299206.8	TSL:1	c.1312C>T	p.Arg438Trp	missense	Exon 8 of 9	ENSP00000299206.4
POLL	ENST00000370169.5	TSL:1	c.1312C>T	p.Arg438Trp	missense	Exon 7 of 8	ENSP00000359188.1

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24444

AN:

152030

Hom.:

2393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0693

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.0359

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.172

GnomAD2 exomes

AF:

0.168

AC:

42107

AN:

251244

AF XY:

0.171

show subpopulations

Gnomad AFR exome

AF:

0.0671

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.235

Gnomad EAS exome

AF:

0.0330

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.200

AC:

292446

AN:

1461044

Hom.:

31057

Cov.:

AF XY:

0.199

AC XY:

144760

AN XY:

726862

show subpopulations

African (AFR)

AF:

0.0621

AC:

2080

AN:

33472

American (AMR)

AF:

0.114

AC:

5103

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

6273

AN:

26128

East Asian (EAS)

AF:

0.0468

AC:

1857

AN:

39700

South Asian (SAS)

AF:

0.128

AC:

11065

AN:

86244

European-Finnish (FIN)

AF:

0.188

AC:

10002

AN:

53290

Middle Eastern (MID)

AF:

0.180

AC:

1036

AN:

5768

European-Non Finnish (NFE)

AF:

0.219

AC:

243544

AN:

1111374

Other (OTH)

AF:

0.190

AC:

11486

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

10849

21698

32548

43397

54246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8064

16128

24192

32256

40320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.161

AC:

24434

AN:

152148

Hom.:

2392

Cov.:

AF XY:

0.158

AC XY:

11723

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0692

AC:

2873

AN:

41530

American (AMR)

AF:

0.158

AC:

2423

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

822

AN:

3472

East Asian (EAS)

AF:

0.0360

AC:

186

AN:

5164

South Asian (SAS)

AF:

0.116

AC:

562

AN:

4826

European-Finnish (FIN)

AF:

0.184

AC:

1942

AN:

10576

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

14994

AN:

67968

Other (OTH)

AF:

0.171

AC:

361

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1063

2127

3190

4254

5317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.204

Hom.:

15505

Bravo

AF:

0.156

TwinsUK

AF:

0.216

AC:

801

ALSPAC

AF:

0.208

AC:

803

ESP6500AA

AF:

0.0742

AC:

327

ESP6500EA

AF:

0.228

AC:

1964

ExAC

AF:

0.168

AC:

20336

Asia WGS

AF:

0.0620

AC:

215

AN:

3478

EpiCase

AF:

0.231

EpiControl

AF:

0.224

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.037

Eigen

Benign

0.11

Eigen_PC

Benign

0.027

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

1.7

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.15

Sift

Uncertain

0.016

Sift4G

Uncertain

0.034

Polyphen

1.0

Vest4

0.13

MPC

0.18

ClinPred

0.042

GERP RS

1.7

Varity_R

0.28

gMVP

0.48

Mutation Taster

=79/21

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over