Genetic Variant NEIL1:c.435-818dupT (chr15-75351274-C-CT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001352519.2(NEIL1):c.100-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 10950 hom., cov: 0)

Exomes 𝑓: 0.22 ( 28 hom. )

Consequence

NEIL1
NM_001352519.2 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0650

Publications

0 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352519.2. 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.435-818dupT	intron	N/A	NP_078884.2	Q96FI4
NEIL1	NM_001256552.1		c.693-818dupT	intron	N/A	NP_001243481.1	Q96FI4
NEIL1	NM_001352520.2		c.129-818dupT	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.435-837_435-836insT	intron	N/A	ENSP00000347170.4	Q96FI4
NEIL1	ENST00000569035.5	TSL:1	c.435-837_435-836insT	intron	N/A	ENSP00000455730.1	Q96FI4
NEIL1	ENST00000866915.1		c.435-837_435-836insT	intron	N/A	ENSP00000536974.1

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

48086

AN:

121070

Hom.:

10964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.383

Gnomad AMR

AF:

0.415

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.542

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.380

GnomAD4 exome

AF:

0.219

AC:

49556

AN:

225920

Hom.:

Cov.:

AF XY:

0.219

AC XY:

28553

AN XY:

130164

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.131

AC:

707

AN:

5408

American (AMR)

AF:

0.233

AC:

3634

AN:

15608

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

1294

AN:

7470

East Asian (EAS)

AF:

0.227

AC:

1796

AN:

7916

South Asian (SAS)

AF:

0.243

AC:

10405

AN:

42794

European-Finnish (FIN)

AF:

0.217

AC:

1953

AN:

8980

Middle Eastern (MID)

AF:

0.179

AC:

144

AN:

806

European-Non Finnish (NFE)

AF:

0.216

AC:

27331

AN:

126372

Other (OTH)

AF:

0.217

AC:

2292

AN:

10566

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.351

Heterozygous variant carriers

2318

4636

6953

9271

11589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

234

468

702

936

1170

<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:

0.397

AC:

48058

AN:

121064

Hom.:

10950

Cov.:

AF XY:

0.390

AC XY:

21953

AN XY:

56336

show subpopulations

African (AFR)

AF:

0.241

AC:

8022

AN:

33282

American (AMR)

AF:

0.415

AC:

4636

AN:

11180

Ashkenazi Jewish (ASJ)

AF:

0.447

AC:

1392

AN:

3114

East Asian (EAS)

AF:

0.490

AC:

1906

AN:

3892

South Asian (SAS)

AF:

0.541

AC:

1946

AN:

3600

European-Finnish (FIN)

AF:

0.345

AC:

1424

AN:

4130

Middle Eastern (MID)

AF:

0.341

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.468

AC:

27726

AN:

59192

Other (OTH)

AF:

0.378

AC:

618

AN:

1636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

1065

2130

3196

4261

5326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.130

Hom.:

282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.065

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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