Genetic Variant NEIL1:c.435-693G>T (chr15-75351418-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024608.4(NEIL1):c.435-693G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 375,086 control chromosomes in the GnomAD database, including 44,096 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 0.44 ( 15386 hom., cov: 28)

Exomes 𝑓: 0.50 ( 28710 hom. )

Consequence

NEIL1
NM_024608.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.54

Publications

12 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

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.435-693G>T	intron	N/A	NP_078884.2	Q96FI4
NEIL1	NM_001256552.1		c.693-693G>T	intron	N/A	NP_001243481.1	Q96FI4
NEIL1	NM_001352520.2		c.129-693G>T	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.435-693G>T	intron	N/A	ENSP00000347170.4	Q96FI4
NEIL1	ENST00000569035.5	TSL:1	c.435-693G>T	intron	N/A	ENSP00000455730.1	Q96FI4
NEIL1	ENST00000866915.1		c.435-693G>T	intron	N/A	ENSP00000536974.1

Frequencies

GnomAD3 genomes

AF:

0.440

AC:

66551

AN:

151292

Hom.:

15390

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.551

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.526

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.476

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.446

GnomAD4 exome

AF:

0.503

AC:

112431

AN:

223676

Hom.:

28710

Cov.:

AF XY:

0.508

AC XY:

64201

AN XY:

126504

show subpopulations

African (AFR)

AF:

0.277

AC:

1514

AN:

5466

American (AMR)

AF:

0.615

AC:

7925

AN:

12880

Ashkenazi Jewish (ASJ)

AF:

0.475

AC:

2450

AN:

5160

East Asian (EAS)

AF:

0.550

AC:

4728

AN:

8600

South Asian (SAS)

AF:

0.553

AC:

24023

AN:

43470

European-Finnish (FIN)

AF:

0.487

AC:

4398

AN:

9034

Middle Eastern (MID)

AF:

0.411

AC:

915

AN:

2224

European-Non Finnish (NFE)

AF:

0.486

AC:

61186

AN:

125984

Other (OTH)

AF:

0.487

AC:

5292

AN:

10858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

2741

5482

8223

10964

13705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.440

AC:

66564

AN:

151410

Hom.:

15386

Cov.:

AF XY:

0.441

AC XY:

32637

AN XY:

73976

show subpopulations

African (AFR)

AF:

0.296

AC:

12183

AN:

41190

American (AMR)

AF:

0.552

AC:

8383

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

1579

AN:

3470

East Asian (EAS)

AF:

0.526

AC:

2691

AN:

5120

South Asian (SAS)

AF:

0.543

AC:

2597

AN:

4784

European-Finnish (FIN)

AF:

0.476

AC:

4986

AN:

10482

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.483

AC:

32752

AN:

67862

Other (OTH)

AF:

0.440

AC:

924

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1766

3532

5299

7065

8831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.459

Hom.:

3423

Bravo

AF:

0.440

Asia WGS

AF:

0.523

AC:

1821

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.13

(source)

DANN

Benign

0.18

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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