dbSNP rs5745909: NEIL1:c.434+34G>A (chr15-75349373-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_024608.4(NEIL1):c.434+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00956 in 1,557,666 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 11 hom., cov: 33)

Exomes 𝑓: 0.0098 ( 78 hom. )

Consequence

NEIL1
NM_024608.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.17

Publications

8 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 15-75349373-G-A is Benign according to our data. Variant chr15-75349373-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1316935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024608.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEIL1	NM_024608.4	MANE Select	c.434+34G>A	intron	N/A	NP_078884.2	Q96FI4
NEIL1	NM_001256552.1		c.692+34G>A	intron	N/A	NP_001243481.1	Q96FI4
NEIL1	NM_001352520.2		c.128+34G>A	intron	N/A	NP_001339449.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEIL1	ENST00000355059.9	TSL:2 MANE Select	c.434+34G>A	intron	N/A	ENSP00000347170.4	Q96FI4
NEIL1	ENST00000569035.5	TSL:1	c.434+34G>A	intron	N/A	ENSP00000455730.1	Q96FI4
NEIL1	ENST00000866915.1		c.434+34G>A	intron	N/A	ENSP00000536974.1

Frequencies

GnomAD3 genomes

AF:

0.00728

AC:

1108

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.00726

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.00716

GnomAD2 exomes

AF:

0.00717

AC:

1455

AN:

202846

AF XY:

0.00729

show subpopulations

Gnomad AFR exome

AF:

0.00163

Gnomad AMR exome

AF:

0.00491

Gnomad ASJ exome

AF:

0.0201

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00242

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.00981

AC:

13784

AN:

1405328

Hom.:

Cov.:

AF XY:

0.00954

AC XY:

6621

AN XY:

693914

show subpopulations

African (AFR)

AF:

0.00146

AC:

AN:

32224

American (AMR)

AF:

0.00490

AC:

199

AN:

40604

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

432

AN:

23102

East Asian (EAS)

AF:

0.00

AC:

AN:

39114

South Asian (SAS)

AF:

0.000125

AC:

AN:

79790

European-Finnish (FIN)

AF:

0.00195

AC:

AN:

45192

Middle Eastern (MID)

AF:

0.00379

AC:

AN:

5540

European-Non Finnish (NFE)

AF:

0.0114

AC:

12330

AN:

1081712

Other (OTH)

AF:

0.0113

AC:

657

AN:

58050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

784

1567

2351

3134

3918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

468

936

1404

1872

2340

<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:

0.00728

AC:

1109

AN:

152338

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

464

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00214

AC:

AN:

41588

American (AMR)

AF:

0.00725

AC:

111

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0117

AC:

797

AN:

68024

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

116

173

231

289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0101

Hom.:

Bravo

AF:

0.00759

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely 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

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.81

(source)

DANN

Benign

0.53

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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