dbSNP rs5745906: NEIL1:p.Gly83Asp (chr15-75349153-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3BP4_StrongBS2

The NM_024608.4(NEIL1):c.248G>A(p.Gly83Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,609,500 control chromosomes in the GnomAD database, including 4 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 0.00077 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 4 hom. )

Consequence

NEIL1
NM_024608.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.14

Publications

30 publications found

Variant links:

Genes affected

NEIL1 (HGNC:18448): (nei like DNA glycosylase 1) This gene is a member of the Nei endonuclease VIII-like gene family which encodes DNA glycosylases. The encoded enzyme participates in the DNA repair pathway by initiating base excision repair by removing damaged bases, primarily oxidized pyrimidines. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

NEIL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.04553938).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEIL1	NM_024608.4 link	c.248G>A	p.Gly83Asp	missense_variant	Exon 2 of 10	ENST00000355059.9	NP_078884.2	Q96FI4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEIL1	ENST00000355059.9 link	c.248G>A	p.Gly83Asp	missense_variant	Exon 2 of 10	2	NM_024608.4	ENSP00000347170.4		Q96FI4

Frequencies

GnomAD3 genomes

AF:

0.000775

AC:

118

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.00122

AC:

300

AN:

246258

AF XY:

0.00111

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00967

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000108

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00106

AC:

1547

AN:

1457124

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

736

AN XY:

725094

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00159

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0108

AC:

282

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.000244

AC:

AN:

49184

Middle Eastern (MID)

AF:

0.000181

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

0.000991

AC:

1102

AN:

1111874

Other (OTH)

AF:

0.00131

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

104

208

312

416

520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.000768

AC:

117

AN:

152376

Hom.:

Cov.:

AF XY:

0.000738

AC XY:

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41600

American (AMR)

AF:

0.000653

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00950

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000955

AC:

AN:

68034

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00132

Hom.:

Bravo

AF:

0.000861

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00175

AC:

ExAC

AF:

0.00123

AC:

149

EpiCase

AF:

0.000981

EpiControl

AF:

0.000889

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.;T;T;T;.;.;T

Eigen

Pathogenic

0.97

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

.;D;D;.;D;D;D;D

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.046

T;T;T;T;T;T;T;T

MetaSVM

Pathogenic

0.86

MutationAssessor

Pathogenic

4.1

H;.;.;H;H;.;.;.

PhyloP100

9.1

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.3

D;D;D;D;D;D;D;D

REVEL

Pathogenic

0.86

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;.;D;D;.;.;.

Vest4

0.94

MVP

0.95

MPC

0.78

ClinPred

0.22

GERP RS

5.4

Varity_R

0.95

gMVP

0.94

Mutation Taster

=16/84

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over